#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Tailored Immune Responses: Novel Effector Helper T Cell Subsets in Protective Immunity


Differentiation of naïve CD4+ cells into functionally distinct effector helper T cell subsets, characterised by distinct “cytokine signatures,” is a cardinal strategy employed by the mammalian immune system to efficiently deal with the rapidly evolving array of pathogenic microorganisms encountered by the host. Since the TH1/TH2 paradigm was first described by Mosmann and Coffman, research in the field of helper T cell biology has grown exponentially with seven functionally unique subsets having now been described. In this review, recent insights into the molecular mechanisms that govern differentiation and function of effector helper T cell subsets will be discussed in the context of microbial infections, with a focus on how these different helper T cell subsets orchestrate immune responses tailored to combat the nature of the pathogenic threat encountered.


Vyšlo v časopise: Tailored Immune Responses: Novel Effector Helper T Cell Subsets in Protective Immunity. PLoS Pathog 10(2): e32767. doi:10.1371/journal.ppat.1003905
Kategorie: Review
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1003905

Souhrn

Differentiation of naïve CD4+ cells into functionally distinct effector helper T cell subsets, characterised by distinct “cytokine signatures,” is a cardinal strategy employed by the mammalian immune system to efficiently deal with the rapidly evolving array of pathogenic microorganisms encountered by the host. Since the TH1/TH2 paradigm was first described by Mosmann and Coffman, research in the field of helper T cell biology has grown exponentially with seven functionally unique subsets having now been described. In this review, recent insights into the molecular mechanisms that govern differentiation and function of effector helper T cell subsets will be discussed in the context of microbial infections, with a focus on how these different helper T cell subsets orchestrate immune responses tailored to combat the nature of the pathogenic threat encountered.


Zdroje

1. ZhuJ, PaulWE (2010) Peripheral CD4+ T-cell differentiation regulated by networks of cytokines and transcription factors. Immunol Rev 238: 247–262.

2. JoffreO, NolteMA, SporriR, Reis e SousaC (2009) Inflammatory signals in dendritic cell activation and the induction of adaptive immunity. Immunol Rev 227: 234–247.

3. MosmannTR, CherwinskiH, BondMW, GiedlinMA, CoffmanRL (1986) Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol 136: 2348–2357.

4. OkoyeIS, WilsonMS (2011) CD4+ T helper 2 cells–microbial triggers, differentiation requirements and effector functions. Immunology 134: 368–377.

5. RoweJH, ErteltJM, WaySS (2012) Foxp3(+) regulatory T cells, immune stimulation and host defence against infection. Immunology 136: 1–10.

6. TakedaA, HamanoS, YamanakaA, HanadaT, IshibashiT, et al. (2003) Cutting edge: role of IL-27/WSX-1 signaling for induction of T-bet through activation of STAT1 during initial Th1 commitment. J Immunol 170: 4886–4890.

7. LighvaniAA, FruchtDM, JankovicD, YamaneH, AlibertiJ, et al. (2001) T-bet is rapidly induced by interferon-gamma in lymphoid and myeloid cells. Proc Natl Acad Sci U S A 98: 15137–15142.

8. HibbertL, PflanzS, De Waal MalefytR, KasteleinRA (2003) IL-27 and IFN-alpha signal via Stat1 and Stat3 and induce T-Bet and IL-12Rbeta2 in naive T cells. J Interferon Cytokine Res 23: 513–522.

9. KamiyaS, OwakiT, MorishimaN, FukaiF, MizuguchiJ, et al. (2004) An indispensable role for STAT1 in IL-27-induced T-bet expression but not proliferation of naive CD4+ T cells. J Immunol 173: 3871–3877.

10. LucasS, GhilardiN, LiJ, de SauvageFJ (2003) IL-27 regulates IL-12 responsiveness of naive CD4+ T cells through Stat1-dependent and -independent mechanisms. Proc Natl Acad Sci U S A 100: 15047–15052.

11. AfkarianM, SedyJR, YangJ, JacobsonNG, CerebN, et al. (2002) T-bet is a STAT1-induced regulator of IL-12R expression in naive CD4+ T cells. Nat Immunol 3: 549–557.

12. SzaboSJ, SullivanBM, StemmannC, SatoskarAR, SleckmanBP, et al. (2002) Distinct effects of T-bet in TH1 lineage commitment and IFN-gamma production in CD4 and CD8 T cells. Science 295: 338–342.

13. ThierfelderWE, van DeursenJM, YamamotoK, TrippRA, SarawarSR, et al. (1996) Requirement for Stat4 in interleukin-12-mediated responses of natural killer and T cells. Nature 382: 171–174.

14. KaplanMH, SunYL, HoeyT, GrusbyMJ (1996) Impaired IL-12 responses and enhanced development of Th2 cells in Stat4-deficient mice. Nature 382: 174–177.

15. SzaboSJ, KimST, CostaGL, ZhangX, FathmanCG, et al. (2000) A novel transcription factor, T-bet, directs Th1 lineage commitment. Cell 100: 655–669.

16. LordGM, RaoRM, ChoeH, SullivanBM, LichtmanAH, et al. (2005) T-bet is required for optimal proinflammatory CD4+ T-cell trafficking. Blood 106: 3432–3439.

17. GroomJR, LusterAD (2011) CXCR3 ligands: redundant, collaborative and antagonistic functions. Immunol Cell Biol 89: 207–215.

18. HsiehCS, MacatoniaSE, TrippCS, WolfSF, O'GarraA, et al. (1993) Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages. Science 260: 547–549.

19. KempM, KurtzhalsJA, BendtzenK, PoulsenLK, HansenMB, et al. (1993) Leishmania donovani-reactive Th1- and Th2-like T-cell clones from individuals who have recovered from visceral leishmaniasis. Infect Immun 61: 1069–1073.

20. SwainSL, McKinstryKK, StruttTM (2012) Expanding roles for CD4(+) T cells in immunity to viruses. Nat Rev Immunol 12: 136–148.

21. MutisT, CornelisseYE, OttenhoffTH (1993) Mycobacteria induce CD4+ T cells that are cytotoxic and display Th1-like cytokine secretion profile: heterogeneity in cytotoxic activity and cytokine secretion levels. Eur J Immunol 23: 2189–2195.

22. HaanenJB, de Waal MalefijtR, ResPC, KraakmanEM, OttenhoffTH, et al. (1991) Selection of a human T helper type 1-like T cell subset by mycobacteria. J Exp Med 174: 583–592.

23. ZhangM, GatelyMK, WangE, GongJ, WolfSF, et al. (1994) Interleukin 12 at the site of disease in tuberculosis. J Clin Invest 93: 1733–1739.

24. de JongR, AltareF, HaagenIA, ElferinkDG, BoerT, et al. (1998) Severe mycobacterial and Salmonella infections in interleukin-12 receptor-deficient patients. Science 280: 1435–1438.

25. AltareF, DurandyA, LammasD, EmileJF, LamhamediS, et al. (1998) Impairment of mycobacterial immunity in human interleukin-12 receptor deficiency. Science 280: 1432–1435.

26. FrohlichA, KisielowJ, SchmitzI, FreigangS, ShamshievAT, et al. (2009) IL-21R on T cells is critical for sustained functionality and control of chronic viral infection. Science 324: 1576–1580.

27. YiJS, DuM, ZajacAJ (2009) A vital role for interleukin-21 in the control of a chronic viral infection. Science 324: 1572–1576.

28. YiJS, IngramJT, ZajacAJ (2010) IL-21 deficiency influences CD8 T cell quality and recall responses following an acute viral infection. J Immunol 185: 4835–4845.

29. SwainSL, WeinbergAD, EnglishM, HustonG (1990) IL-4 directs the development of Th2-like helper effectors. J Immunol 145: 3796–3806.

30. Le GrosG, Ben-SassonSZ, SederR, FinkelmanFD, PaulWE (1990) Generation of interleukin 4 (IL-4)-producing cells in vivo and in vitro: IL-2 and IL-4 are required for in vitro generation of IL-4-producing cells. J Exp Med 172: 921–929.

31. KaplanMH, SchindlerU, SmileyST, GrusbyMJ (1996) Stat6 is required for mediating responses to IL-4 and for development of Th2 cells. Immunity 4: 313–319.

32. ShimodaK, van DeursenJ, SangsterMY, SarawarSR, CarsonRT, et al. (1996) Lack of IL-4-induced Th2 response and IgE class switching in mice with disrupted Stat6 gene. Nature 380: 630–633.

33. TakedaK, TanakaT, ShiW, MatsumotoM, MinamiM, et al. (1996) Essential role of Stat6 in IL-4 signalling. Nature 380: 627–630.

34. ZhuJ, GuoL, WatsonCJ, Hu-LiJ, PaulWE (2001) Stat6 is necessary and sufficient for IL-4's role in Th2 differentiation and cell expansion. J Immunol 166: 7276–7281.

35. ZhengW, FlavellRA (1997) The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells. Cell 89: 587–596.

36. ZhangDH, CohnL, RayP, BottomlyK, RayA (1997) Transcription factor GATA-3 is differentially expressed in murine Th1 and Th2 cells and controls Th2-specific expression of the interleukin-5 gene. J Biol Chem 272: 21597–21603.

37. OuyangW, LohningM, GaoZ, AssenmacherM, RanganathS, et al. (2000) Stat6-independent GATA-3 autoactivation directs IL-4-independent Th2 development and commitment. Immunity 12: 27–37.

38. PaulWE (2010) What determines Th2 differentiation, in vitro and in vivo? Immunol Cell Biol 88: 236–239.

39. MikhakZ, FukuiM, FarsidjaniA, MedoffBD, TagerAM, et al. (2009) Contribution of CCR4 and CCR8 to antigen-specific T(H)2 cell trafficking in allergic pulmonary inflammation. J Allergy Clin Immunol 123: 67–e63, 67-73, e63.

40. SallustoF, MackayCR, LanzavecchiaA (1997) Selective expression of the eotaxin receptor CCR3 by human T helper 2 cells. Science 277: 2005–2007.

41. PearceEJ, CasparP, GrzychJM, LewisFA, SherA (1991) Downregulation of Th1 cytokine production accompanies induction of Th2 responses by a parasitic helminth, Schistosoma mansoni. J Exp Med 173: 159–166.

42. ElseKJ, HultnerL, GrencisRK (1992) Cellular immune responses to the murine nematode parasite Trichuris muris. II. Differential induction of TH-cell subsets in resistant versus susceptible mice. Immunology 75: 232–237.

43. SchrammG, HaasH (2010) Th2 immune response against Schistosoma mansoni infection. Microbes Infect 12: 881–888.

44. MaizelsRM, HewitsonJP, SmithKA (2012) Susceptibility and immunity to helminth parasites. Curr Opin Immunol 24: 459–466.

45. HarringtonLE, HattonRD, ManganPR, TurnerH, MurphyTL, et al. (2005) Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat Immunol 6: 1123–1132.

46. ParkH, LiZ, YangXO, ChangSH, NurievaR, et al. (2005) A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat Immunol 6: 1133–1141.

47. GalloE, KatzmanS, VillarinoAV (2012) IL-13-producing Th1 and Th17 cells characterize adaptive responses to both self and foreign antigens. Eur J Immunol 42: 2322–2328.

48. RaymondM, VanVQ, WakaharaK, RubioM, SarfatiM (2011) Lung dendritic cells induce T(H)17 cells that produce T(H)2 cytokines, express GATA-3, and promote airway inflammation. J Allergy Clin Immunol 128: 192–e196, 192-201, e196.

49. BonifaceK, BlumenscheinWM, Brovont-PorthK, McGeachyMJ, BashamB, et al. (2010) Human Th17 cells comprise heterogeneous subsets including IFN-gamma-producing cells with distinct properties from the Th1 lineage. J Immunol 185: 679–687.

50. ZielinskiCE, MeleF, AschenbrennerD, JarrossayD, RonchiF, et al. (2012) Pathogen-induced human TH17 cells produce IFN-gamma or IL-10 and are regulated by IL-1beta. Nature 484: 514–518.

51. VeldhoenM, HockingRJ, AtkinsCJ, LocksleyRM, StockingerB (2006) TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 24: 179–189.

52. ManganPR, HarringtonLE, O'QuinnDB, HelmsWS, BullardDC, et al. (2006) Transforming growth factor-beta induces development of the T(H)17 lineage. Nature 441: 231–234.

53. ZhouL, IvanovII, SpolskiR, MinR, ShenderovK, et al. (2007) IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol 8: 967–974.

54. YangXO, PanopoulosAD, NurievaR, ChangSH, WangD, et al. (2007) STAT3 regulates cytokine-mediated generation of inflammatory helper T cells. J Biol Chem 282: 9358–9363.

55. HarrisTJ, GrossoJF, YenHR, XinH, KortylewskiM, et al. (2007) Cutting edge: an in vivo requirement for STAT3 signaling in TH17 development and TH17-dependent autoimmunity. J Immunol 179: 4313–4317.

56. IvanovII, McKenzieBS, ZhouL, TadokoroCE, LepelleyA, et al. (2006) The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126: 1121–1133.

57. YangXO, PappuBP, NurievaR, AkimzhanovA, KangHS, et al. (2008) T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma. Immunity 28: 29–39.

58. WeiL, LaurenceA, EliasKM, O'SheaJJ (2007) IL-21 is produced by Th17 cells and drives IL-17 production in a STAT3-dependent manner. J Biol Chem 282: 34605–34610.

59. NurievaR, YangXO, MartinezG, ZhangY, PanopoulosAD, et al. (2007) Essential autocrine regulation by IL-21 in the generation of inflammatory T cells. Nature 448: 480–483.

60. GutcherI, DonkorMK, MaQ, RudenskyAY, FlavellRA, et al. (2011) Autocrine transforming growth factor-beta1 promotes in vivo Th17 cell differentiation. Immunity 34: 396–408.

61. GhoreschiK, LaurenceA, YangXP, TatoCM, McGeachyMJ, et al. (2010) Generation of pathogenic T(H)17 cells in the absence of TGF-beta signalling. Nature 467: 967–971.

62. LeeY, AwasthiA, YosefN, QuintanaFJ, XiaoS, et al. (2012) Induction and molecular signature of pathogenic TH17 cells. Nat Immunol 13: 991–999.

63. YamazakiT, YangXO, ChungY, FukunagaA, NurievaR, et al. (2008) CCR6 regulates the migration of inflammatory and regulatory T cells. J Immunol 181: 8391–8401.

64. YuJJ, GaffenSL (2008) Interleukin-17: a novel inflammatory cytokine that bridges innate and adaptive immunity. Front Biosci 13: 170–177.

65. LockhartE, GreenAM, FlynnJL (2006) IL-17 production is dominated by gammadelta T cells rather than CD4 T cells during Mycobacterium tuberculosis infection. J Immunol 177: 4662–4669.

66. TakatoriH, KannoY, WatfordWT, TatoCM, WeissG, et al. (2009) Lymphoid tissue inducer-like cells are an innate source of IL-17 and IL-22. J Exp Med 206: 35–41.

67. GladiatorA, WanglerN, Trautwein-WeidnerK, LeibundGut-LandmannS (2013) Cutting edge: IL-17-secreting innate lymphoid cells are essential for host defense against fungal infection. J Immunol 190: 521–525.

68. DoisneJM, SoulardV, BecourtC, AmniaiL, HenrotP, et al. (2011) Cutting edge: crucial role of IL-1 and IL-23 in the innate IL-17 response of peripheral lymph node NK1.1- invariant NKT cells to bacteria. J Immunol 186: 662–666.

69. CuaDJ, TatoCM (2010) Innate IL-17-producing cells: the sentinels of the immune system. Nat Rev Immunol 10: 479–489.

70. RubinoSJ, GeddesK, GirardinSE (2012) Innate IL-17 and IL-22 responses to enteric bacterial pathogens. Trends Immunol 33: 112–118.

71. YeP, GarveyPB, ZhangP, NelsonS, BagbyG, et al. (2001) Interleukin-17 and lung host defense against Klebsiella pneumoniae infection. Am J Respir Cell Mol Biol 25: 335–340.

72. HappelKI, DubinPJ, ZhengM, GhilardiN, LockhartC, et al. (2005) Divergent roles of IL-23 and IL-12 in host defense against Klebsiella pneumoniae. J Exp Med 202: 761–769.

73. WangF, XuJ, LiaoY, WangY, LiuC, et al. (2011) Tim-3 ligand galectin-9 reduces IL-17 level and accelerates Klebsiella pneumoniae infection. Cell Immunol 269: 22–28.

74. IshigameH, KakutaS, NagaiT, KadokiM, NambuA, et al. (2009) Differential roles of interleukin-17A and -17F in host defense against mucoepithelial bacterial infection and allergic responses. Immunity 30: 108–119.

75. IvanovII, AtarashiK, ManelN, BrodieEL, ShimaT, et al. (2009) Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139: 485–498.

76. HigginsSC, JarnickiAG, LavelleEC, MillsKH (2006) TLR4 mediates vaccine-induced protective cellular immunity to Bordetella pertussis: role of IL-17-producing T cells. J Immunol 177: 7980–7989.

77. AndreasenC, PowellDA, CarbonettiNH (2009) Pertussis toxin stimulates IL-17 production in response to Bordetella pertussis infection in mice. PLoS ONE 4: e7079.

78. YuJJ, RuddyMJ, WongGC, SfintescuC, BakerPJ, et al. (2007) An essential role for IL-17 in preventing pathogen-initiated bone destruction: recruitment of neutrophils to inflamed bone requires IL-17 receptor-dependent signals. Blood 109: 3794–3802.

79. YuJJ, RuddyMJ, ContiHR, BoonanantanasarnK, GaffenSL (2008) The interleukin-17 receptor plays a gender-dependent role in host protection against Porphyromonas gingivalis-induced periodontal bone loss. Infect Immun 76: 4206–4213.

80. LuY-J, GrossJ, BogaertD, FinnA, BagradeL, et al. (2008) Interleukin-17A mediates acquired immunity to pneumococcal colonization. PLoS Pathog 4: e1000159.

81. ZhangZ, ClarkeTB, WeiserJN (2009) Cellular effectors mediating Th17-dependent clearance of pneumococcal colonization in mice. J Clin Invest 119: 1899–1909.

82. McGeachyMJ, ChenY, TatoCM, LaurenceA, Joyce-ShaikhB, et al. (2009) The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo. Nat Immunol 10: 314–324.

83. GeddesK, RubinoSJ, MagalhaesJG, StreutkerC, Le BourhisL, et al. (2011) Identification of an innate T helper type 17 response to intestinal bacterial pathogens. Nat Med 17: 837–844.

84. BuonocoreS, AhernPP, UhligHH, IvanovII, LittmanDR, et al. (2010) Innate lymphoid cells drive interleukin-23-dependent innate intestinal pathology. Nature 464: 1371–1375.

85. PriceAE, ReinhardtRL, LiangH-E, LocksleyRM (2012) Marking and quantifying IL-17A-producing cells in vivo. PLoS ONE 7: e39750.

86. SuttonCE, MielkeLA, MillsKH (2012) IL-17-producing gammadelta T cells and innate lymphoid cells. Eur J Immunol 42: 2221–2231.

87. Hernandez-SantosN, GaffenSL (2012) Th17 cells in immunity to Candida albicans. Cell Host Microbe 11: 425–435.

88. Acosta-RodriguezEV, RivinoL, GeginatJ, JarrossayD, GattornoM, et al. (2007) Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat Immunol 8: 639–646.

89. EyerichK, FoersterS, RomboldS, SeidlHP, BehrendtH, et al. (2008) Patients with chronic mucocutaneous candidiasis exhibit reduced production of Th17-associated cytokines IL-17 and IL-22. J Invest Dermatol 128: 2640–2645.

90. MilnerJD, BrenchleyJM, LaurenceA, FreemanAF, HillBJ, et al. (2008) Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome. Nature 452: 773–776.

91. MaCS, ChewGY, SimpsonN, PriyadarshiA, WongM, et al. (2008) Deficiency of Th17 cells in hyper IgE syndrome due to mutations in STAT3. J Exp Med 205: 1551–1557.

92. MinegishiY, SaitoM, TsuchiyaS, TsugeI, TakadaH, et al. (2007) Dominant-negative mutations in the DNA-binding domain of STAT3 cause hyper-IgE syndrome. Nature 448: 1058–1062.

93. GrimbacherB, HollandSM, GallinJI, GreenbergF, HillSC, et al. (1999) Hyper-IgE syndrome with recurrent infections–an autosomal dominant multisystem disorder. N Engl J Med 340: 692–702.

94. HuangW, NaL, FidelPL, SchwarzenbergerP (2004) Requirement of interleukin-17A for systemic anti-Candida albicans host defense in mice. J Infect Dis 190: 624–631.

95. FarahCS, HuY, RimintonS, AshmanRB (2006) Distinct roles for interleukin-12p40 and tumour necrosis factor in resistance to oral candidiasis defined by gene-targeting. Oral Microbiol Immunol 21: 252–255.

96. ContiHR, ShenF, NayyarN, StocumE, SunJN, et al. (2009) Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis. J Exp Med 206: 299–311.

97. HoAW, ShenF, ContiHR, PatelN, ChildsEE, et al. (2010) IL-17RC is required for immune signaling via an extended SEF/IL-17R signaling domain in the cytoplasmic tail. J Immunol 185: 1063–1070.

98. KagamiS, RizzoHL, KurtzSE, MillerLS, BlauveltA (2010) IL-23 and IL-17A, but not IL-12 and IL-22, are required for optimal skin host defense against Candida albicans. J Immunol 185: 5453–5462.

99. AntachopoulosC, WalshTJ (2012) Immunotherapy of Cryptococcus infections. Clin Microbiol Infect 18: 126–133.

100. ZelanteT, BozzaS, De LucaA, D'AngeloC, BonifaziP, et al. (2009) Th17 cells in the setting of Aspergillus infection and pathology. Med Mycol 47 Suppl 1: S162–169.

101. RudnerXL, HappelKI, YoungEA, ShellitoJE (2007) Interleukin-23 (IL-23)-IL-17 cytokine axis in murine Pneumocystis carinii infection. Infect Immun 75: 3055–3061.

102. Hernandez-SantosN, HupplerAR, PetersonAC, KhaderSA, McKennaKC, et al. (2013) Th17 cells confer long-term adaptive immunity to oral mucosal Candida albicans infections. Mucosal Immunol 6: 900–910.

103. ChenK, McAleerJP, LinY, PatersonDL, ZhengM, et al. (2011) Th17 cells mediate clade-specific, serotype-independent mucosal immunity. Immunity 35: 997–1009.

104. WuthrichM, GernB, HungCY, ErslandK, RoccoN, et al. (2011) Vaccine-induced protection against 3 systemic mycoses endemic to North America requires Th17 cells in mice. J Clin Invest 121: 554–568.

105. KumarP, ChenK, KollsJK (2013) Th17 cell based vaccines in mucosal immunity. Curr Opin Immunol 25: 373–380.

106. KhaderSA, GopalR (2010) IL-17 in protective immunity to intracellular pathogens. Virulence 1: 423–427.

107. WoolardMD, HensleyLL, KawulaTH, FrelingerJA (2008) Respiratory Francisella tularensis live vaccine strain infection induces Th17 cells and prostaglandin E2, which inhibits generation of gamma interferon-positive T cells. Infect Immun 76: 2651–2659.

108. LinY, RitcheaS, LogarA, SlightS, MessmerM, et al. (2009) Interleukin-17 is required for T helper 1 cell immunity and host resistance to the intracellular pathogen Francisella tularensis. Immunity 31: 799–810.

109. BaiH, ChengJ, GaoX, JoyeeAG, FanY, et al. (2009) IL-17/Th17 promotes type 1 T cell immunity against pulmonary intracellular bacterial infection through modulating dendritic cell function. J Immunol 183: 5886–5895.

110. UmemuraM, YahagiA, HamadaS, BegumMD, WatanabeH, et al. (2007) IL-17-mediated regulation of innate and acquired immune response against pulmonary Mycobacterium bovis bacille Calmette-Guerin infection. J Immunol 178: 3786–3796.

111. WuQ, MartinRJ, RinoJG, BreedR, TorresRM, et al. (2007) IL-23-dependent IL-17 production is essential in neutrophil recruitment and activity in mouse lung defense against respiratory Mycoplasma pneumoniae infection. Microbes Infect 9: 78–86.

112. GodinezI, RaffatelluM, ChuH, PaixaoTA, HanedaT, et al. (2009) Interleukin-23 orchestrates mucosal responses to Salmonella enterica serotype Typhimurium in the intestine. Infect Immun 77: 387–398.

113. RaffatelluM, SantosRL, VerhoevenDE, GeorgeMD, WilsonRP, et al. (2008) Simian immunodeficiency virus-induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut. Nat Med 14: 421–428.

114. SuryawanshiA, Veiga-PargaT, RajasagiNK, ReddyPB, SehrawatS, et al. (2011) Role of IL-17 and Th17 cells in herpes simplex virus-induced corneal immunopathology. J Immunol 187: 1919–1930.

115. HouW, KangHS, KimBS (2009) Th17 cells enhance viral persistence and inhibit T cell cytotoxicity in a model of chronic virus infection. J Exp Med 206: 313–328.

116. OyoshiMK, ElkhalA, KumarL, ScottJE, KoduruS, et al. (2009) Vaccinia virus inoculation in sites of allergic skin inflammation elicits a vigorous cutaneous IL-17 response. Proc Natl Acad Sci U S A 106: 14954–14959.

117. McKinstryKK, StruttTM, BuckA, CurtisJD, DibbleJP, et al. (2009) IL-10 deficiency unleashes an influenza-specific Th17 response and enhances survival against high-dose challenge. J Immunol 182: 7353–7363.

118. KellyMN, KollsJK, HappelK, SchwartzmanJD, SchwarzenbergerP, et al. (2005) Interleukin-17/interleukin-17 receptor-mediated signaling is important for generation of an optimal polymorphonuclear response against Toxoplasma gondii infection. Infect Immun 73: 617–621.

119. TallimaH, SalahM, GuirguisFR, El RidiR (2009) Transforming growth factor-beta and Th17 responses in resistance to primary murine schistosomiasis mansoni. Cytokine 48: 239–245.

120. RutitzkyLI, Lopes da RosaJR, StadeckerMJ (2005) Severe CD4 T cell-mediated immunopathology in murine schistosomiasis is dependent on IL-12p40 and correlates with high levels of IL-17. J Immunol 175: 3920–3926.

121. RutitzkyLI, StadeckerMJ (2006) CD4 T cells producing pro-inflammatory interleukin-17 mediate high pathology in schistosomiasis. Mem Inst Oswaldo Cruz 101 Suppl 1: 327–330.

122. MoffittKL, GierahnTM, LuY-J, GouveiaP, AldersonM, et al. (2011) T(H)17-based vaccine design for prevention of Streptococcus pneumoniae colonization. Cell Host Microbe 9: 158–165.

123. DuhenT, GeigerR, JarrossayD, LanzavecchiaA, SallustoF (2009) Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells. Nat Immunol 10: 857–863.

124. TrifariS, KaplanCD, TranEH, CrellinNK, SpitsH (2009) Identification of a human helper T cell population that has abundant production of interleukin 22 and is distinct from T(H)-17, T(H)1 and T(H)2 cells. Nat Immunol 10: 864–871.

125. SonnenbergGF, FouserLA, ArtisD (2011) Border patrol: regulation of immunity, inflammation and tissue homeostasis at barrier surfaces by IL-22. Nat Immunol 12: 383–390.

126. RamirezJ-M, BrembillaNC, SorgO, ChicheporticheR, MatthesT, et al. (2010) Activation of the aryl hydrocarbon receptor reveals distinct requirements for IL-22 and IL-17 production by human T helper cells. Eur J Immunol 40: 2450–2459.

127. BrembillaNC, RamirezJ-M, ChicheporticheR, SorgO, SauratJ-H, et al. (2011) In vivo dioxin favors interleukin-22 production by human CD4+ T cells in an aryl hydrocarbon receptor (AhR)-dependent manner. PLoS ONE 6: e18741.

128. TachiiriA, ImamuraR, WangY, FukuiM, UmemuraM, et al. (2003) Genomic structure and inducible expression of the IL-22 receptor alpha chain in mice. Genes Immun 4: 153–159.

129. WolkK, KunzS, WitteE, FriedrichM, AsadullahK, et al. (2004) IL-22 increases the innate immunity of tissues. Immunity 21: 241–254.

130. LiangSC, TanXY, LuxenbergDP, KarimR, Dunussi-JoannopoulosK, et al. (2006) Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med 203: 2271–2279.

131. WolkK, WitteE, WallaceE, DockeWD, KunzS, et al. (2006) IL-22 regulates the expression of genes responsible for antimicrobial defense, cellular differentiation, and mobility in keratinocytes: a potential role in psoriasis. Eur J Immunol 36: 1309–1323.

132. ZhengY, ValdezPA, DanilenkoDM, HuY, SaSM, et al. (2008) Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat Med 14: 282–289.

133. AujlaSJ, ChanYR, ZhengM, FeiM, AskewDJ, et al. (2008) IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia. Nat Med 14: 275–281.

134. WitteE, WitteK, WarszawskaK, SabatR, WolkK (2010) Interleukin-22: a cytokine produced by T, NK and NKT cell subsets, with importance in the innate immune defense and tissue protection. Cytokine Growth Factor Rev 21: 365–379.

135. LiuY, YangB, ZhouM, LiL, ZhouH, et al. (2009) Memory IL-22-producing CD4+ T cells specific for Candida albicans are present in humans. Eur J Immunol 39: 1472–1479.

136. NgWF, von DelwigA, CarmichaelAJ, ArkwrightPD, AbinunM, et al. (2010) Impaired T(H)17 responses in patients with chronic mucocutaneous candidiasis with and without autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. J Allergy Clin Immunol 126: 1006–1004, 1006-1015, 1015, e1001-1004.

137. van der MeerJW, van de VeerdonkFL, JoostenLA, KullbergBJ, NeteaMG (2010) Severe Candida spp. infections: new insights into natural immunity. Int J Antimicrob Agents 36 Suppl 2: S58–62.

138. EyerichS, WagenerJ, WenzelV, ScarponiC, PenninoD, et al. (2011) IL-22 and TNF-alpha represent a key cytokine combination for epidermal integrity during infection with Candida albicans. Eur J Immunol 41: 1894–1901.

139. De LucaA, ZelanteT, D'AngeloC, ZagarellaS, FallarinoF, et al. (2010) IL-22 defines a novel immune pathway of antifungal resistance. Mucosal Immunol 3: 361–373.

140. WilsonMS, FengCG, BarberDL, YarovinskyF, CheeverAW, et al. (2010) Redundant and pathogenic roles for IL-22 in mycobacterial, protozoan, and helminth infections. J Immunol 184: 4378–4390.

141. ZenewiczLA, YancopoulosGD, ValenzuelaDM, MurphyAJ, KarowM, et al. (2007) Interleukin-22 but not interleukin-17 provides protection to hepatocytes during acute liver inflammation. Immunity 27: 647–659.

142. GuoH, TophamDJ (2010) Interleukin-22 (IL-22) production by pulmonary Natural Killer cells and the potential role of IL-22 during primary influenza virus infection. J Virol 84: 7750–7759.

143. MunozM, HeimesaatMM, DankerK, StruckD, LohmannU, et al. (2009) Interleukin (IL)-23 mediates Toxoplasma gondii-induced immunopathology in the gut via matrixmetalloproteinase-2 and IL-22 but independent of IL-17. J Exp Med 206: 3047–3059.

144. IvanovS, RennesonJ, FontaineJ, BarthelemyA, PagetC, et al. (2013) Interleukin-22 reduces lung inflammation during influenza A virus infection and protects against secondary bacterial infection. J Virol 87: 6911–6924.

145. PociaskDA, SchellerEV, MandalapuS, McHughKJ, EnelowRI, et al. (2013) IL-22 is essential for lung epithelial repair following influenza infection. Am J Pathol 182: 1286–1296.

146. GuabirabaR, BesnardAG, MarquesRE, MailletI, FagundesCT, et al. (2013) IL-22 modulates IL-17A production and controls inflammation and tissue damage in experimental dengue infection. Eur J Immunol 43: 1529–1544.

147. BehrendsJ, RenauldJ-C, EhlersS, HölscherC (2013) IL-22 is mainly produced by IFNγ-secreting cells but is dispensable for host protection against Mycobacterium tuberculosis infection. PLoS ONE 8: e57379.

148. ScribaTJ, KalsdorfB, AbrahamsDA, IsaacsF, HofmeisterJ, et al. (2008) Distinct, specific IL-17- and IL-22-producing CD4+ T cell subsets contribute to the human anti-mycobacterial immune response. J Immunol 180: 1962–1970.

149. QingK, FengWW, FanY, LiLY, MinXY, et al. (2012) Increased Expressions of IL-22 and Th22 cells in the coxsackievirus B3-Induced mice acute viral myocarditis. Virol J 9: 232.

150. BasuR, O'QuinnDB, SilbergerDJ, SchoebTR, FouserL, et al. (2012) Th22 cells are an important source of IL-22 for host protection against enteropathogenic bacteria. Immunity 37: 1061–1075.

151. GoswamiR, KaplanMH (2011) A brief history of IL-9. J Immunol 186: 3283–3288.

152. GessnerA, BlumH, RollinghoffM (1993) Differential regulation of IL-9-expression after infection with Leishmania major in susceptible and resistant mice. Immunobiology 189: 419–435.

153. FaulknerH, RenauldJ-C, Van SnickJ, GrencisRK (1998) Interleukin-9 enhances resistance to the intestinal nematode Trichuris muris. Infect Immun 66: 3832–3840.

154. FaulknerH, HumphreysN, RenauldJ-C, Van SnickJ, GrencisR (1997) Interleukin-9 is involved in host protective immunity to intestinal nematode infection. Eur J Immunol 27: 2536–2540.

155. DugasB, RenauldJC, PeneJ, BonnefoyJY, Peti-FrereC, et al. (1993) Interleukin-9 potentiates the interleukin-4-induced immunoglobulin (IgG, IgM and IgE) production by normal human B lymphocytes. Eur J Immunol 23: 1687–1692.

156. Petit-FrereC, DugasB, BraquetP, Mencia-HuertaJM (1993) Interleukin-9 potentiates the interleukin-4-induced IgE and IgG1 release from murine B lymphocytes. Immunology 79: 146–151.

157. LiH, RostamiA (2010) IL-9: basic biology, signaling pathways in CD4+ T cells and implications for autoimmunity. J Neuroimmune Pharmacol 5: 198–209.

158. DardalhonV, AwasthiA, KwonH, GalileosG, GaoW, et al. (2008) IL-4 inhibits TGF-beta-induced Foxp3+ T cells and, together with TGF-beta, generates IL-9+ IL-10+ Foxp3(−) effector T cells. Nat Immunol 9: 1347–1355.

159. VeldhoenM, UyttenhoveC, van SnickJ, HelmbyH, WestendorfA, et al. (2008) Transforming growth factor-beta ‘reprograms’ the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset. Nat Immunol 9: 1341–1346.

160. YangXO, ZhangH, KimBS, NiuX, PengJ, et al. (2013) The signaling suppressor CIS controls proallergic T cell development and allergic airway inflammation. Nat Immunol 14: 732–740.

161. UyttenhoveC, BrombacherF, Van SnickJ (2010) TGF-beta interactions with IL-1 family members trigger IL-4-independent IL-9 production by mouse CD4(+) T cells. Eur J Immunol 40: 2230–2235.

162. SchmittE, KleinM, BoppT (2013) Th9 cells, new players in adaptive immunity. Trends Immunol E-pub ahead of print.

163. PerumalNB, KaplanMH (2011) Regulating Il9 transcription in T helper cells. Trends Immunol 32: 146–150.

164. ChangHC, SehraS, GoswamiR, YaoW, YuQ, et al. (2010) The transcription factor PU.1 is required for the development of IL-9-producing T cells and allergic inflammation. Nat Immunol 11: 527–534.

165. StaudtV, BothurE, KleinM, LingnauK, ReuterS, et al. (2010) Interferon-regulatory factor 4 is essential for the developmental program of T helper 9 cells. Immunity 33: 192–202.

166. JabeenR, GoswamiR, AweO, KulkarniA, NguyenET, et al. (2013) Th9 cell development requires a BATF-regulated transcriptional network. J Clin Invest E-pub ahead of print.

167. KaraEE, ComerfordI, BastowCR, FenixKA, LitchfieldW, et al. (2013) Distinct chemokine receptor axes regulate Th9 cell trafficking to allergic and autoimmune inflammatory sites. J Immunol 191: 1110–1117.

168. KhanWI, RichardM, AkihoH, BlennerhassetPA, HumphreysNE, et al. (2003) Modulation of intestinal muscle contraction by interleukin-9 (IL-9) or IL-9 neutralization: correlation with worm expulsion in murine nematode infections. Infect Immun 71: 2430–2438.

169. Licona-LimonP, Henao-MejiaJ, TemannAU, GaglianiN, Licona-LimonI, et al. (2013) Th9 cells drive host immunity against gastrointestinal worm infection. Immunity 39: 744–757.

170. TurnerJE, MorrisonPJ, WilhelmC, WilsonM, AhlforsH, et al. (2013) IL-9-mediated survival of type 2 innate lymphoid cells promotes damage control in helminth-induced lung inflammation. J Exp Med 210: 2951–2965.

171. TownsendJM, FallonGP, MatthewsJD, SmithP, JolinEH, et al. (2000) IL-9-deficient mice establish fundamental roles for IL-9 in pulmonary mastocytosis and goblet cell hyperplasia but not T cell development. Immunity 13: 573–583.

172. LiE, ZhouP, PetrinZ, SingerSM (2004) Mast cell-dependent control of Giardia lamblia infections in mice. Infect Immun 72: 6642–6649.

173. FallonPG, JolinHE, SmithP, EmsonCL, TownsendMJ, et al. (2002) IL-4 induces characteristic Th2 responses even in the combined absence of IL-5, IL-9, and IL-13. Immunity 17: 7–17.

174. YamasakiA, SalehA, KoussihL, MuroS, HalaykoAJ, et al. (2010) IL-9 induces CCL11 expression via STAT3 signalling in human airway smooth muscle cells. PLoS ONE 5: e9178.

175. GounniAS, HamidQ, RahmanSM, HoeckJ, YangJ, et al. (2004) IL-9-mediated induction of eotaxin1/CCL11 in human airway smooth muscle cells. J Immunol 173: 2771–2779.

176. LouahedJ, ZhouY, MaloyWL, RaniPU, WeissC, et al. (2001) Interleukin 9 promotes influx and local maturation of eosinophils. Blood 97: 1035–1042.

177. McNamaraPS, FlanaganBF, BaldwinLM, NewlandP, HartCA, et al. (2004) Interleukin 9 production in the lungs of infants with severe respiratory syncytial virus bronchiolitis. Lancet 363: 1031–1037.

178. DoddJS, LumE, GouldingJ, MuirR, Van SnickJ, et al. (2009) IL-9 regulates pathology during primary and memory responses to respiratory syncytial virus infection. J Immunol 183: 7006–7013.

179. GrohmannU, Van SnickJ, CampanileF, SillaS, GiampietriA, et al. (2000) IL-9 protects mice from Gram-negative bacterial shock: suppression of TNF-alpha, IL-12, and IFN-gamma, and induction of IL-10. J Immunol 164: 4197–4203.

180. YeZ-J, YuanM-L, ZhouQ, DuR-H, YangW-B, et al. (2012) Differentiation and recruitment of Th9 cells stimulated by pleural mesothelial cells in human Mycobacterium tuberculosis infection. PLoS ONE 7: e31710.

181. NoelleRJ, NowakEC (2010) Cellular sources and immune functions of interleukin-9. Nat Rev Immunol 10: 683–687.

182. WilhelmC, HirotaK, StieglitzB, Van SnickJ, TolainiM, et al. (2011) An IL-9 fate reporter demonstrates the induction of an innate IL-9 response in lung inflammation. Nat Immunol 12: 1071–1077.

183. NuttSL, TarlintonDM (2011) Germinal center B and follicular helper T cells: siblings, cousins or just good friends? Nat Immunol 12: 472–477.

184. CrottyS (2011) Follicular helper CD4 T cells (TFH). Annu Rev Immunol 29: 621–663.

185. JohnstonRJ, PoholekAC, DiToroD, YusufI, EtoD, et al. (2009) Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation. Science 325: 1006–1010.

186. NurievaRI, ChungY, MartinezGJ, YangXO, TanakaS, et al. (2009) Bcl6 mediates the development of T follicular helper cells. Science 325: 1001–1005.

187. YuD, RaoS, TsaiLM, LeeSK, HeY, et al. (2009) The transcriptional repressor Bcl-6 directs T follicular helper cell lineage commitment. Immunity 31: 457–468.

188. KingIL, MohrsM (2009) IL-4-producing CD4+ T cells in reactive lymph nodes during helminth infection are T follicular helper cells. J Exp Med 206: 1001–1007.

189. HsuHC, YangP, WangJ, WuQ, MyersR, et al. (2008) Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice. Nat Immunol 9: 166–175.

190. LintermanMA, BeatonL, YuD, RamiscalRR, SrivastavaM, et al. (2010) IL-21 acts directly on B cells to regulate Bcl-6 expression and germinal center responses. J Exp Med 207: 353–363.

191. LeeSK, SilvaDG, MartinJL, PratamaA, HuX, et al. (2012) Interferon-gamma excess leads to pathogenic accumulation of follicular helper T cells and germinal centers. Immunity 37: 880–892.

192. ChtanovaT, TangyeSG, NewtonR, FrankN, HodgeMR, et al. (2004) T follicular helper cells express a distinctive transcriptional profile, reflecting their role as non-Th1/Th2 effector cells that provide help for B cells. J Immunol 173: 68–78.

193. NurievaRI, ChungY, HwangD, YangXO, KangHS, et al. (2008) Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages. Immunity 29: 138–149.

194. KimCH, LimHW, KimJR, RottL, HillsamerP, et al. (2004) Unique gene expression program of human germinal center T helper cells. Blood 104: 1952–1960.

195. KroenkeMA, EtoD, LocciM, ChoM, DavidsonT, et al. (2012) Bcl6 and Maf cooperate to instruct human follicular helper CD4 T cell differentiation. J Immunol 188: 3734–3744.

196. BreitfeldD, OhlL, KremmerE, EllwartJ, SallustoF, et al. (2000) Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production. J Exp Med 192: 1545–1552.

197. SchaerliP, WillimannK, LangAB, LippM, LoetscherP, et al. (2000) CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function. J Exp Med 192: 1553–1562.

198. MaCS, DeenickEK, BattenM, TangyeSG (2012) The origins, function, and regulation of T follicular helper cells. J Exp Med 209: 1241–1253.

199. FazilleauN, McHeyzer-WilliamsLJ, RosenH, McHeyzer-WilliamsMG (2009) The function of follicular helper T cells is regulated by the strength of T cell antigen receptor binding. Nat Immunol 10: 375–384.

200. DeenickEK, ChanA, MaCS, GattoD, SchwartzbergPL, et al. (2010) Follicular helper T cell differentiation requires continuous antigen presentation that is independent of unique B cell signaling. Immunity 33: 241–253.

201. EtoD, LaoC, DiToroD, BarnettB, EscobarTC, et al. (2011) IL-21 and IL-6 are critical for different aspects of B cell immunity and redundantly induce optimal follicular helper CD4 T cell (Tfh) differentiation. PLoS ONE 6: e17739.

202. MaCS, AveryDT, ChanA, BattenM, BustamanteJ, et al. (2012) Functional STAT3 deficiency compromises the generation of human T follicular helper cells. Blood 119: 3997–4008.

203. ChoiYS, EtoD, YangJA, LaoC, CrottyS (2013) Cutting edge: STAT1 is required for IL-6-mediated Bcl6 induction for early follicular helper cell differentiation. J Immunol 190: 3049–3053.

204. MaCS, SuryaniS, AveryDT, ChanA, NananR, et al. (2009) Early commitment of naive human CD4(+) T cells to the T follicular helper (T(FH)) cell lineage is induced by IL-12. Immunol Cell Biol 87: 590–600.

205. SchmittN, BustamanteJ, BourderyL, BentebibelSE, Boisson-DupuisS, et al. (2013) IL-12 receptor beta1 deficiency alters in vivo T follicular helper cell response in humans. Blood 121: 3375–3385.

206. SchmittN, MoritaR, BourderyL, BentebibelSE, ZurawskiSM, et al. (2009) Human dendritic cells induce the differentiation of interleukin-21-producing T follicular helper-like cells through interleukin-12. Immunity 31: 158–169.

207. NakayamadaS, KannoY, TakahashiH, JankovicD, LuKT, et al. (2011) Early Th1 cell differentiation is marked by a Tfh cell-like transition. Immunity 35: 919–931.

208. Ballesteros-TatoA, RandallTD (2014) Priming of T follicular helper cells by dendritic cells. Immunol Cell Biol 92: 22–27.

209. HaynesNM, AllenCD, LesleyR, AnselKM, KilleenN, et al. (2007) Role of CXCR5 and CCR7 in follicular Th cell positioning and appearance of a programmed cell death gene-1high germinal center-associated subpopulation. J Immunol 179: 5099–5108.

210. BaumjohannD, OkadaT, AnselKM (2011) Cutting edge: distinct waves of BCL6 expression during T follicular helper cell development. J Immunol 187: 2089–2092.

211. LiuYJ, JoshuaDE, WilliamsGT, SmithCA, GordonJ, et al. (1989) Mechanism of antigen-driven selection in germinal centres. Nature 342: 929–931.

212. ChoeJ, KimHS, ZhangX, ArmitageRJ, ChoiYS (1996) Cellular and molecular factors that regulate the differentiation and apoptosis of germinal center B cells. Anti-Ig down-regulates Fas expression of CD40 ligand-stimulated germinal center B cells and inhibits Fas-mediated apoptosis. J Immunol 157: 1006–1016.

213. ZotosD, CoquetJM, ZhangY, LightA, D'CostaK, et al. (2010) IL-21 regulates germinal center B cell differentiation and proliferation through a B cell-intrinsic mechanism. J Exp Med 207: 365–378.

214. AruffoA, FarringtonM, HollenbaughD, LiX, MilatovichA, et al. (1993) The CD40 ligand, gp39, is defective in activated T cells from patients with X-linked hyper-IgM syndrome. Cell 72: 291–300.

215. OzakiK, SpolskiR, EttingerR, KimHP, WangG, et al. (2004) Regulation of B cell differentiation and plasma cell generation by IL-21, a novel inducer of Blimp-1 and Bcl-6. J Immunol 173: 5361–5371.

216. EttingerR, SimsGP, FairhurstAM, RobbinsR, da SilvaYS, et al. (2005) IL-21 induces differentiation of human naive and memory B cells into antibody-secreting plasma cells. J Immunol 175: 7867–7879.

217. KuchenS, RobbinsR, SimsGP, ShengC, PhillipsTM, et al. (2007) Essential role of IL-21 in B cell activation, expansion, and plasma cell generation during CD4+ T cell-B cell collaboration. J Immunol 179: 5886–5896.

218. BryantVL, MaCS, AveryDT, LiY, GoodKL, et al. (2007) Cytokine-mediated regulation of human B cell differentiation into Ig-secreting cells: predominant role of IL-21 produced by CXCR5+ T follicular helper cells. J Immunol 179: 8180–8190.

219. DiSantoJP, BonnefoyJY, GauchatJF, FischerA, de Saint BasileG (1993) CD40 ligand mutations in x-linked immunodeficiency with hyper-IgM. Nature 361: 541–543.

220. AllenRC, ArmitageRJ, ConleyME, RosenblattH, JenkinsNA, et al. (1993) CD40 ligand gene defects responsible for X-linked hyper-IgM syndrome. Science 259: 990–993.

221. QiH, CannonsJL, KlauschenF, SchwartzbergPL, GermainRN (2008) SAP-controlled T-B cell interactions underlie germinal centre formation. Nature 455: 764–769.

222. CannonsJL, QiH, LuKT, DuttaM, Gomez-RodriguezJ, et al. (2010) Optimal germinal center responses require a multistage T cell:B cell adhesion process involving integrins, SLAM-associated protein, and CD84. Immunity 32: 253–265.

223. YusufI, KageyamaR, MonticelliL, JohnstonRJ, DitoroD, et al. (2010) Germinal center T follicular helper cell IL-4 production is dependent on signaling lymphocytic activation molecule receptor (CD150). J Immunol 185: 190–202.

224. RezaeiN, MahmoudiE, AghamohammadiA, DasR, NicholsKE (2011) X-linked lymphoproliferative syndrome: a genetic condition typified by the triad of infection, immunodeficiency and lymphoma. Br J Haematol 152: 13–30.

225. MohrsK, WakilAE, KilleenN, LocksleyRM, MohrsM (2005) A two-step process for cytokine production revealed by IL-4 dual-reporter mice. Immunity 23: 419–429.

226. ReinhardtRL, LiangH-E, LocksleyRM (2009) Cytokine-secreting follicular T cells shape the antibody repertoire. Nat Immunol 10: 385–393.

227. LuthjeK, KalliesA, ShimohakamadaY, GTTB, LightA, et al. (2012) The development and fate of follicular helper T cells defined by an IL-21 reporter mouse. Nat Immunol 13: 491–498.

228. LiuX, YanX, ZhongB, NurievaRI, WangA, et al. (2012) Bcl6 expression specifies the T follicular helper cell program in vivo. J Exp Med 209: 1841–1824, 1841-1852, S1841-1824.

229. ZaretskyAG, TaylorJJ, KingIL, MarshallFA, MohrsM, et al. (2009) T follicular helper cells differentiate from Th2 cells in response to helminth antigens. J Exp Med 206: 991–999.

230. FaheyLM, WilsonEB, ElsaesserH, FistonichCD, McGavernDB, et al. (2011) Viral persistence redirects CD4 T cell differentiation toward T follicular helper cells. J Exp Med 208: 987–999.

231. HirotaK, TurnerJE, VillaM, DuarteJH, DemengeotJ, et al. (2013) Plasticity of Th17 cells in Peyer's patches is responsible for the induction of T cell-dependent IgA responses. Nat Immunol 14: 372–379.

232. SoghoianDZ, StreeckH (2010) Cytolytic CD4(+) T cells in viral immunity. Expert Rev Vaccines 9: 1453–1463.

233. SutoA, KashiwakumaD, KagamiS, HiroseK, WatanabeN, et al. (2008) Development and characterization of IL-21-producing CD4+ T cells. J Exp Med 205: 1369–1379.

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2014 Číslo 2
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#