Characterisation of Regulatory T Cells in Nasal Associated Lymphoid Tissue in Children: Relationships with Pneumococcal Colonization

English version České info

Regulatory T cells (Treg) diminish immune responses to microbial infection, which may contribute to preventing inflammation-related local tissue damage and autoimmunity but may also contribute to chronicity of infection. Nasopharyngeal carriage of pneumococcus is common in young children and can persist for long periods but it is unknown whether the presence of Treg in the nasopharynx contributes to this persistence. We have investigated the numbers and activities of Foxp3+Treg in adenoidal tissues and their association with pneumococcal carriage in children. Expression of Treg cell-related markers including Foxp3, CD25, CD39, CD127 and CLTA4 were analysed by flow-cytometry in adenoidal mononuclear cells (MNC) and PBMC from children. Unfractionated MNC or Treg-depleted MNC were stimulated with a pneumococcal whole cell antigen (WCA) and T cell proliferation measured. Cytokine production by MNC was measured using a cytometric bead array. Higher numbers of CD25^highFoxp3^high Treg expressing higher CD39 and CTLA4 were found in adenoidal MNC than in PBMC. Children with pneumococcus positive nasopharyngeal cultures had higher proportions of Treg and expressed higher levels of CD39 and CTLA-4 than those who were culture negative (−). WCA induced adenoidal Treg proliferation which produce IL10 but not IL17, and CD4 T cell proliferation in Treg-depleted MNC was greater in pneumococcal culture positive than negative children. Significant numbers of Treg with an effector/memory phenotype which possess a potent inhibitory effect, exist in adenoidal tissue. The association of pneumococcal carriage with an increased frequency of adenoidal Treg suggests that Treg in nasal-associated lymphoid tissue (NALT) may contribute to the persistence of pneumococcus in children. Further studies to determine what component and mechanisms are involved in the promotion of Treg in NALT may lead to novel therapeutic or vaccination strategy against upper respiratory infection.

Vyšlo v časopise: Characterisation of Regulatory T Cells in Nasal Associated Lymphoid Tissue in Children: Relationships with Pneumococcal Colonization. PLoS Pathog 7(8): e32767. doi:10.1371/journal.ppat.1002175
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002175

Souhrn

Zdroje

1. SakaguchiSSakaguchiS 2004 Naturally arising CD4+ regulatory t cells for immunologic self-tolerance and negative control of immune responses. Annu Rev Immunol 22 531 562

2. BelkaidYBelkaidY 2008 Role of Foxp3-positive regulatory T cells during infection. Eur J Immunol 38 918 921

3. ChenWJinWHardegenNLeiKJLiL 2003 Conversion of peripheral CD4+CD25− naive T cells to CD4+CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 198 1875 1886

4. SeddikiNSantner-NananBMartinsonJZaundersJSassonS 2006 Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T cells. J Exp Med 203 1693 1700

5. LiuWPutnamALXu-YuZSzotGLLeeMR 2006 CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells. J Exp Med 203 1701 1711

6. FletcherJMLonerganRCostelloeLKinsellaKMoranB 2009 CD39+Foxp3+ regulatory T Cells suppress pathogenic Th17 cells and are impaired in multiple sclerosis. J Immunol 183 7602 7610

7. IzcueACoombesJLPowrieFIzcueACoombesJL 2006 Regulatory T cells suppress systemic and mucosal immune activation to control intestinal inflammation. Immunol Rev 212 256 271

8. ZhengYManzottiCNBurkeFDussablyLQureshiO 2008 Acquisition of suppressive function by activated human CD4+ CD25− T cells is associated with the expression of CTLA-4 not FoxP3. J Immunol 181 1683 1691

9. WingKOnishiYPrieto-MartinPYamaguchiTMiyaraM 2008 CTLA-4 control over Foxp3+ regulatory T cell function. Science 322 271 275

10. BorsellinoGKleinewietfeldMDi MitriDSternjakADiamantiniA 2007 Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression. Blood 110 1225 1232

11. RouseBTSarangiPPSuvasSRouseBTSarangiPP 2006 Regulatory T cells in virus infections. Immunol Rev 212 272 286

12. EppleHJLoddenkemperCKunkelDTrogerHMaulJ 2006 Mucosal but not peripheral FOXP3+ regulatory T cells are highly increased in untreated HIV infection and normalize after suppressive HAART. Blood 108 3072 3078

13. KinterALHennesseyMBellAKernSLinY 2004 CD25(+)CD4(+) regulatory T cells from the peripheral blood of asymptomatic HIV-infected individuals regulate CD4(+) and CD8(+) HIV-specific T cell immune responses in vitro and are associated with favorable clinical markers of disease status. J Exp Med 200 331 343

14. BolacchiFSinistroACiapriniCDeminFCapozziM 2006 Increased hepatitis C virus (HCV)-specific CD4+CD25+ regulatory T lymphocytes and reduced HCV-specific CD4+ T cell response in HCV-infected patients with normal versus abnormal alanine aminotransferase levels. Clin & Exp Immunol 144 188 196

15. Guyot-RevolVInnesJAHackforthSHinksTLalvaniA 2006 Regulatory T cells are expanded in blood and disease sites in patients with tuberculosis. Am J Respir Crit Care Med 173 803 810

16. RaghavanSHolmgrenJRaghavanSHolmgrenJ 2005 CD4+CD25+ suppressor T cells regulate pathogen induced inflammation and disease. FEMS Immunol & Med Microbiol 44 121 127

17. ZhangQBernatonieneJBagradeLPollardAJMitchellTJ 2006 Serum and mucosal antibody responses to pneumococcal protein antigens in children: relationships with carriage status. Eur J Immunol 36 46 57

18. ZhangQBernatonieneJBagradeLClarkeEPatonJC 2007 Low CD4 T cell immunity to pneumolysin is associated with nasopharyngeal carriage of pneumococci in children. J Infect Dis 195 1194 1202

19. BrandtzaegP 2003 Immunology of tonsils and adenoids: everything the ENT surgeon needs to know. Int J Pediatr Otorhinolaryngol 67 Suppl 1 S69 S76

20. KiyonoHFukuyamaSKiyonoHFukuyamaS 2004 NALT- versus Peyer's-patch-mediated mucosal immunity. Nat Rev Immunol 4 699 710

21. McMichaelAJRowland-JonesS 2001 Cellular immune responses to HIV. Nature 410 980 987

22. CooperAMCooperAM 2009 Cell-mediated immune responses in tuberculosis. Annu Rev Immunol 27 393 422

23. MalleyRTrzcinskiKSrivastavaAThompsonCMAndersonPW 2005 CD4 T cells mediate antibody-independent acquired immunity to pneumococcal colonization. Proc Natl Acad Sci USA 102 4848 4853

24. McCoolTLWeiserJN 2004 Limited role of antibody in clearance of Streptococcus pneumoniae in a murine model of colonization. Infect Immun 72 5807 5813

25. KadiogluACowardWColstonMJHewittCRAndrewPW 2004 CD4-T-lymphocyte interactions with pneumolysin and pneumococci suggest a crucial protective role in the host response to pneumococcal infection. Infect Immun 72 2689 2697

26. MalleyRLipsitchMStackASaladinoRFleisherG 2001 Intranasal immunization with killed unencapsulated whole cells prevents colonization and invasive disease by capsulated pneumococci. Infect Immun 69 4870 4873

27. SungCKLiHClaverysJPMorrisonDASungCK 2001 An rpsL cassette, janus, for gene replacement through negative selection in Streptococcus pneumoniae. Appl & Environ Microbiol 67 5190 5196

28. ZhangQBagradeLClarkeEPatonJCNunezDA 2010 Bacterial lipoproteins differentially regulate human primary and memory CD4+ T and B cell responses to pneumococcal protein antigens through Toll-like receptor 2. J Infect Dis 201 1753 1763

29. ZhangQBernatonieneJBagradeLPatonJCMitchellTJ 2006 Regulation of mucosal antibody production to pneumococcal protein antigens by T-cell derived IFNg and IL-10 in children. Infect Immun 74 4735 4743

30. SakaguchiSMiyaraMCostantinoCMHaflerDASakaguchiS 2010 FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol 10 490 500

31. ValmoriDMerloASouleimanianNEHesdorfferCSAyyoubM 2005 A peripheral circulating compartment of natural naive CD4 Tregs. J Clin Invest 115 1953 1962

32. MiyaraMYoshiokaYKitohAShimaTWingK 2009 Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. Immunity 30 899 911

33. FritzschingBOberleNPaulyEGeffersRBuerJ 2006 Naive regulatory T cells: a novel subpopulation defined by resistance toward CD95L-mediated cell death. Blood 108 3371 3378

34. Baecher-AllanCBrownJAFreemanGJHaflerDABaecher-AllanC 2001 CD4+CD25high regulatory cells in human peripheral blood. J Immunol 167 1245 1253

35. AnderssonJBoassoANilssonJZhangRShireNJ 2005 The prevalence of regulatory T cells in lymphoid tissue is correlated with viral load in HIV-infected patients. J Immunol 174 3143 3147

36. ShafianiSTucker-HeardGKariyoneATakatsuKUrdahlKB 2010 Pathogen-specific regulatory T cells delay the arrival of effector T cells in the lung during early tuberculosis. J Exp Med 207 1409 1420

37. NilssonJBoassoAVelillaPAZhangRVaccariM 2006 HIV-1-driven regulatory T-cell accumulation in lymphoid tissues is associated with disease progression in HIV/AIDS. Blood 108 3808 3817

38. BelkaidYPiccirilloCAMendezSShevachEMSacksDL 2002 CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity. Nature 420 502 507

39. MaizelsRMMaizelsRM 2005 Infections and allergy - helminths, hygiene and host immune regulation. Curr Opin Immunol 17 656 661

40. LuYJGrossJBogaertDFinnABagradeL 2008 Interleukin-17A mediates acquired immunity to pneumococcal colonization. PLoS Pathogens 4 e1000159

41. MaiJWangHYangXFMaiJWangH 2010 Th 17 cells interplay with Foxp3+ Tregs in regulation of inflammation and autoimmunity. Front Biosci 15 986 1006

42. KinterAMcNallyJRigginLJacksonRRobyG 2007 Suppression of HIV-specific T cell activity by lymph node CD25+ regulatory T cells from HIV-infected individuals. Proc Natl Acad Sci USA 104 3390 3395

43. SakaguchiSSakaguchiS 2003 Regulatory T cells: mediating compromises between host and parasite. Nat Immunol 4 10 11