Dynamic Functional Modulation of CD4 T Cell Recall Responses Is Dependent on the Inflammatory Environment of the Secondary Stimulus

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A key to the development of strategies for manipulating immune responses is the identification of the factors that regulate the generation of memory T cells. Many vaccination strategies rely on multiple injections to boost memory cell numbers, yet the factors that regulate the function and survival of memory T cells following multiple challenges are not fully understood. Here, we define key parameters during boosting that regulate the functional capacity and longevity of memory T cells. We report that the boosting of highly functional and long-lived memory T cells is dependent on both the activation environment and duration of the secondary challenge. Our findings demonstrate that T cells have functional plasticity that depends on the inflammatory environment of the secondary T cell activation and have direct bearing on the design of strategies aimed at generating highly functional memory T cells.

Vyšlo v časopise: Dynamic Functional Modulation of CD4 T Cell Recall Responses Is Dependent on the Inflammatory Environment of the Secondary Stimulus. PLoS Pathog 10(5): e32767. doi:10.1371/journal.ppat.1004137
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004137

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Zdroje

1. WilliamsMA, BevanMJ (2007) Effector and Memory CTL Differentiation. Annual Review of Immunology 25: 171–192.

2. van LeeuwenEM, SprentJ, SurhCD (2009) Generation and maintenance of memory CD4(+) T Cells. Curr Opin Immunol 21: 167–172.

3. WilliamsMA, RavkovEV, BevanMJ (2008) Rapid culling of the CD4+ T cell repertoire in the transition from effector to memory. Immunity 28: 533–545.

4. KimC, WilsonT, FischerKF, WilliamsMA (2013) Sustained Interactions between T Cell Receptors and Antigens Promote the Differentiation of CD4(+) Memory T Cells. Immunity 39: 508–520.

5. BrogdonJL, LeitenbergD, BottomlyK (2002) The potency of TCR signaling differentially regulates NFATc/p activity and early IL-4 transcription in naive CD4+ T cells. Journal of immunology 168: 3825–3832.

6. 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. Nature immunology 10: 375–384.

7. GettAV, SallustoF, LanzavecchiaA, GeginatJ (2003) T cell fitness determined by signal strength. Nat Immunol 4: 355–360.

8. LeeHM, BautistaJL, Scott-BrowneJ, MohanJF, HsiehCS (2012) A broad range of self-reactivity drives thymic regulatory T cell selection to limit responses to self. Immunity 37: 475–486.

9. LeitenbergD, BottomlyK (1999) Regulation of naive T cell differentiation by varying the potency of TCR signal transduction. Seminars in immunology 11: 283–292.

10. MoranAE, HolzapfelKL, XingY, CunninghamNR, MaltzmanJS, et al. (2011) T cell receptor signal strength in Treg and iNKT cell development demonstrated by a novel fluorescent reporter mouse. The Journal of Experimental Medicine 208: 1279–1289.

11. TuboNJ, PaganAJ, TaylorJJ, NelsonRW, LinehanJL, et al. (2013) Single naive CD4+ T cells from a diverse repertoire produce different effector cell types during infection. Cell 153: 785–796.

12. CrottyS, JohnstonRJ, SchoenbergerSP (2010) Effectors and memories: Bcl-6 and Blimp-1 in T and B lymphocyte differentiation. Nat Immunol 11: 114–120.

13. JohnstonRJ, ChoiYS, DiamondJA, YangJA, CrottyS (2012) STAT5 is a potent negative regulator of TFH cell differentiation. The Journal of Experimental Medicine 209: 243–250.

14. LuthjeK, KalliesA, ShimohakamadaY, BelzGT, 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.

15. PepperM, PaganAJ, IgyartoBZ, TaylorJJ, JenkinsMK (2011) Opposing signals from the Bcl6 transcription factor and the interleukin-2 receptor generate T helper 1 central and effector memory cells. Immunity 35: 583–595.

16. WeberJP, FuhrmannF, HutloffA (2012) T-follicular helper cells survive as long-term memory cells. Eur J Immunol 42: 1981–1988.

17. SlifkaMK, WhittonJL (2001) Functional avidity maturation of CD8+ T cells without selection of higher affinity TCR. Nat Immunol 2: 711–717.

18. WhitmireJK, BenningN, WhittonJL (2006) Precursor Frequency, Nonlinear Proliferation, and Functional Maturation of Virus-Specific CD4+ T Cells. J Immunol 176: 3028–3036.

19. WirthTC, XueHH, RaiD, SabelJT, BairT, et al. (2010) Repetitive antigen stimulation induces stepwise transcriptome diversification but preserves a core signature of memory CD8(+) T cell differentiation. Immunity 33: 128–140.

20. WherryEJ, TeichgraberV, BeckerTC, MasopustD, KaechSM, et al. (2003) Lineage relationship and protective immunity of memory CD8 T cell subsets. Nat Immunol 4: 225–234.

21. BachmannMF, WolintP, SchwarzK, JagerP, OxeniusA (2005) Functional properties and lineage relationship of CD8+ T cell subsets identified by expression of IL-7 receptor alpha and CD62L. J Immunol 175: 4686–4696.

22. BachmannMF, WolintP, SchwarzK, OxeniusA (2005) Recall proliferation potential of memory CD8+ T cells and antiviral protection. J Immunol 175: 4677–4685.

23. OlsonJA, McDonald-HymanC, JamesonSC, HamiltonSE (2013) Effector-like CD8(+) T Cells in the Memory Population Mediate Potent Protective Immunity. Immunity 38: 1250–1260.

24. RicherMJ, NolzJC, HartyJT (2013) Pathogen-specific inflammatory milieux tune the antigen sensitivity of CD8(+) T cells by enhancing T cell receptor signaling. Immunity 38: 140–152.

25. RaueHP, BeadlingC, HaunJ, SlifkaMK (2013) Cytokine-mediated programmed proliferation of virus-specific CD8(+) memory T cells. Immunity 38: 131–139.

26. JabbariA, HartyJT (2006) Secondary memory CD8+ T cells are more protective but slower to acquire a central-memory phenotype. J Exp Med 203: 919–932.

27. NolzJC, HartyJT (2011) Protective capacity of memory CD8+ T cells is dictated by antigen exposure history and nature of the infection. Immunity 34: 781–793.

28. WhitmireJK, EamB, WhittonJL (2008) Tentative T cells: memory cells are quick to respond, but slow to divide. PLoS Pathog 4: e1000041.

29. StruttTM, McKinstryKK, KuangY, BradleyLM, SwainSL (2012) Memory CD4+ T-cell-mediated protection depends on secondary effectors that are distinct from and superior to primary effectors. Proc Natl Acad Sci U S A 109: E2551–2560.

30. RavkovEV, WilliamsMA (2009) The Magnitude of CD4+ T Cell Recall Responses Is Controlled by the Duration of the Secondary Stimulus. The Journal of Immunology 183: 2382–2389.

31. KimC, JayDC, WilliamsMA (2012) Stability and function of secondary Th1 memory cells are dependent on the nature of the secondary stimulus. J Immunol 189: 2348–2355.

32. KhanolkarA, WilliamsMA, HartyJT (2013) Antigen experience shapes phenotype and function of memory Th1 cells. PLoS One 8: e65234.

33. DarrahPA, PatelDT, De LucaPM, LindsayRW, DaveyDF, et al. (2007) Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major. Nat Med 13: 843–850.

34. SederRA, DarrahPA, RoedererM (2008) T-cell quality in memory and protection: implications for vaccine design. Nat Rev Immunol 8: 247–258.

35. HomannD, LewickiH, BrooksD, EberleinJ, Mallet-DesigneV, et al. (2007) Mapping and restriction of a dominant viral CD4+ T cell core epitope by both MHC class I and MHC class II. Virology 363: 113–123.

36. FouldsKE, ShenH (2006) Clonal Competition Inhibits the Proliferation and Differentiation of Adoptively Transferred TCR Transgenic CD4 T Cells in Response to Infection. J Immunol 176: 3037–3043.

37. FouldsKE, ZenewiczLA, ShedlockDJ, JiangJ, TroyAE, et al. (2002) Cutting Edge: CD4 and CD8 T Cells Are Intrinsically Different in Their Proliferative Responses. J Immunol 168: 1528–1532.

38. ChiangGG, SeftonBM (2001) Specific dephosphorylation of the Lck tyrosine protein kinase at Tyr-394 by the SHP-1 protein-tyrosine phosphatase. J Biol Chem 276: 23173–23178.

39. PlasDR, JohnsonR, PingelJT, MatthewsRJ, DaltonM, et al. (1996) Direct regulation of ZAP-70 by SHP-1 in T cell antigen receptor signaling. Science 272: 1173–1176.

40. StefanovaI, HemmerB, VergelliM, MartinR, BiddisonWE, et al. (2003) TCR ligand discrimination is enforced by competing ERK positive and SHP-1 negative feedback pathways. Nat Immunol 4: 248–254.

41. ZhangZ, KobayashiS, BorczukAC, LeidnerRS, LaframboiseT, et al. (2010) Dual specificity phosphatase 6 (DUSP6) is an ETS-regulated negative feedback mediator of oncogenic ERK signaling in lung cancer cells. Carcinogenesis 31: 577–586.

42. LiG, YuM, LeeWW, TsangM, KrishnanE, et al. (2012) Decline in miR-181a expression with age impairs T cell receptor sensitivity by increasing DUSP6 activity. Nat Med 18: 1518–1524.

43. ZhangJ, BardosT, LiD, GalI, VermesC, et al. (2002) Cutting edge: regulation of T cell activation threshold by CD28 costimulation through targeting Cbl-b for ubiquitination. J Immunol 169: 2236–2240.

44. LoeserS, PenningerJM (2007) Regulation of peripheral T cell tolerance by the E3 ubiquitin ligase Cbl-b. Semin Immunol 19: 206–214.

45. AuerbuchV, BrockstedtDG, Meyer-MorseN, O'RiordanM, PortnoyDA (2004) Mice lacking the type I interferon receptor are resistant to Listeria monocytogenes. J Exp Med 200: 527–533.

46. O'ConnellRM, SahaSK, VaidyaSA, BruhnKW, MirandaGA, et al. (2004) Type I interferon production enhances susceptibility to Listeria monocytogenes infection. J Exp Med 200: 437–445.

47. TeijaroJR, NgC, LeeAM, SullivanBM, SheehanKC, et al. (2013) Persistent LCMV infection is controlled by blockade of type I interferon signaling. Science 340: 207–211.

48. Havenar-DaughtonC, KolumamGA, Murali-KrishnaK (2006) Cutting Edge: The Direct Action of Type I IFN on CD4 T Cells Is Critical for Sustaining Clonal Expansion in Response to a Viral but Not a Bacterial Infection. J Immunol 176: 3315–3319.

49. KolumamGA, ThomasS, ThompsonLJ, SprentJ, Murali-KrishnaK (2005) Type I interferons act directly on CD8 T cells to allow clonal expansion and memory formation in response to viral infection. J Exp Med 202: 637–650.

50. KimC, WilliamsMA (2010) Nature and nurture: T-cell receptor-dependent and T-cell receptor-independent differentiation cues in the selection of the memory T-cell pool. Immunology 131: 310–317.

51. ChandokMR, OkoyeFI, NdejembiMP, FarberDL (2007) A biochemical signature for rapid recall of memory CD4 T cells. J Immunol 179: 3689–3698.

52. LaiW, YuM, HuangMN, OkoyeF, KeeganAD, et al. (2011) Transcriptional control of rapid recall by memory CD4 T cells. J Immunol 187: 133–140.

53. OxeniusA, BachmannMF, ZinkernagelRM, HengartnerH (1998) Virus-specific MHC-class II-restricted TCR-transgenic mice: effects on humoral and cellular immune responses after viral infection. Eur J Immunol 28: 390–400.

54. AhmedR, SalmiA, ButlerLD, ChillerJM, OldstoneMB (1984) Selection of genetic variants of lymphocytic choriomeningitis virus in spleens of persistently infected mice. Role in suppression of cytotoxic T lymphocyte response and viral persistence. J Exp Med 160: 521–540.

55. BihlF, PecheurJ, BreartB, PouponG, CazarethJ, et al. (2010) Primed antigen-specific CD4+ T cells are required for NK cell activation in vivo upon Leishmania major infection. J Immunol 185: 2174–2181.

56. Vom BergJ, ProkopS, MillerKR, ObstJ, KalinRE, et al. (2012) Inhibition of IL-12/IL-23 signaling reduces Alzheimer's disease-like pathology and cognitive decline. Nat Med 18: 1812–1819.

57. SheehanKC, LaiKS, DunnGP, BruceAT, DiamondMS, et al. (2006) Blocking monoclonal antibodies specific for mouse IFN-alpha/beta receptor subunit 1 (IFNAR-1) from mice immunized by in vivo hydrodynamic transfection. J Interferon Cytokine Res 26: 804–819.

58. MempelTR, HenricksonSE, von AndrianUH (2004) T-cell priming by dendritic cells in lymph nodes occurs in three distinct phases. Nature 427: 154–159.