MHC Class II Restricted Innate-Like Double Negative T Cells Contribute to Optimal Primary and Secondary Immunity to

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Although it is generally believed that CD4+ T cells mediate anti-Leishmania immunity, some studies suggest that CD3+CD4−CD8− (double negative, DN) T cells may play a more important role in regulating primary anti-Leishmania immunity. Here, we report that DN T cells extensively proliferate and produce effector cytokines in mice following primary and secondary L. major infections. Leishmania-reactive DN T cells utilize αβ T cell receptor (TCR) and are restricted by MHC class II molecules. Strikingly, DN T cells from healed mice display functional characteristics of protective anti-Leishmania memory-like cells: rapid and extensive proliferation, effector cytokine production in vitro and in vivo, and accelerated parasite control following secondary L. major challenge. These results directly identify DN T cells as important players in protective primary and secondary anti-L. major immunity in experimental cutaneous leishmaniasis.

Vyšlo v časopise: MHC Class II Restricted Innate-Like Double Negative T Cells Contribute to Optimal Primary and Secondary Immunity to. PLoS Pathog 10(9): e32767. doi:10.1371/journal.ppat.1004396
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004396

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Zdroje

1. ReithingerR, DujardinJC, LouzirH, PirmezC, AlexanderB, et al. (2007) Cutaneous leishmaniasis. Lancet Infect Dis 7: 581–596.

2. SacksD, Noben-TrauthN (2002) The immunology of susceptibility and resistance to Leishmania major in mice. Nat Rev Immunol 2: 845–858.

3. PetersNC, EgenJG, SecundinoN, DebrabantA, KimblinN, et al. (2008) In vivo imaging reveals an essential role for neutrophils in leishmaniasis transmitted by sand flies. Science 321: 970–974.

4. ZaphC, UzonnaJ, BeverleySM, ScottP (2004) Central memory T cells mediate long-term immunity to Leishmania major in the absence of persistent parasites. Nature medicine 10: 1104–1110.

5. LiuD, ZhangT, MarshallAJ, OkkenhaugK, VanhaesebroeckB, et al. (2009) The p110delta isoform of phosphatidylinositol 3-kinase controls susceptibility to Leishmania major by regulating expansion and tissue homing of regulatory T cells. Journal of immunology 183: 1921–1933.

6. KayeP, ScottP (2011) Leishmaniasis: complexity at the host-pathogen interface. Nature reviews Microbiology 9: 604–615.

7. SwihartK, FruthU, MessmerN, HugK, BehinR, et al. (1995) Mice from a genetically resistant background lacking the interferon gamma receptor are susceptible to infection with Leishmania major but mount a polarized T helper cell 1-type CD4+ T cell response. The Journal of experimental medicine 181: 961–971.

8. WangZE, ReinerSL, ZhengS, DaltonDK, LocksleyRM (1994) CD4+ effector cells default to the Th2 pathway in interferon gamma-deficient mice infected with Leishmania major. The Journal of experimental medicine 179: 1367–1371.

9. WeiXQ, CharlesIG, SmithA, UreJ, FengGJ, et al. (1995) Altered immune responses in mice lacking inducible nitric oxide synthase. Nature 375: 408–411.

10. LocksleyRM, ReinerSL, HatamF, LittmanDR, KilleenN (1993) Helper T cells without CD4: control of leishmaniasis in CD4-deficient mice. Science 261: 1448–1451.

11. AntonelliLR, DutraWO, OliveiraRR, TorresKC, GuimaraesLH, et al. (2006) Disparate immunoregulatory potentials for double-negative (CD4- CD8-) alpha beta and gamma delta T cells from human patients with cutaneous leishmaniasis. Infect Immun 74: 6317–6323.

12. GollobKJ, AntonelliLR, FariaDR, KeesenTS, DutraWO (2008) Immunoregulatory mechanisms and CD4-CD8- (double negative) T cell subpopulations in human cutaneous leishmaniasis: a balancing act between protection and pathology. Int Immunopharmacol 8: 1338–1343.

13. Alexandre-PiresG, de BritoMT, AlgueroC, MartinsC, RodriguesOR, et al. (2010) Canine leishmaniasis. Immunophenotypic profile of leukocytes in different compartments of symptomatic, asymptomatic and treated dogs. Veterinary immunology and immunopathology 137: 275–283.

14. Lezama-DavilaCM, GallagherG (1995) CD4+, CD8+ and CD4- CD8- T cell-subsets can confer protection against Leishmania m. mexicana infection. Mem Inst Oswaldo Cruz 90: 51–58.

15. HillhouseEE, BeauchampC, Chabot-RoyG, DugasV, LesageS (2010) Interleukin-10 limits the expansion of immunoregulatory CD4-CD8- T cells in autoimmune-prone non-obese diabetic mice. Immunology and cell biology 88: 771–780.

16. VoelklS, GaryR, MackensenA (2011) Characterization of the immunoregulatory function of human TCR-alphabeta+ CD4- CD8- double-negative T cells. European journal of immunology 41: 739–748.

17. PriatelJJ, UttingO, TehHS (2001) TCR/self-antigen interactions drive double-negative T cell peripheral expansion and differentiation into suppressor cells. Journal of immunology 167: 6188–6194.

18. WangR, Wang-ZhuY, GreyH (2002) Interactions between double positive thymocytes and high affinity ligands presented by cortical epithelial cells generate double negative thymocytes with T cell regulatory activity. Proceedings of the National Academy of Sciences of the United States of America 99: 2181–2186.

19. D'AcquistoF, CromptonT (2011) CD3+CD4-CD8- (double negative) T cells: saviours or villains of the immune response? Biochemical pharmacology 82: 333–340.

20. PrinsRM, IncardonaF, LauR, LeeP, ClausS, et al. (2004) Characterization of defective CD4-CD8- T cells in murine tumors generated independent of antigen specificity. J Immunol 172: 1602–1611.

21. FordMS, ZhangZX, ChenW, ZhangL (2006) Double-negative T regulatory cells can develop outside the thymus and do not mature from CD8+ T cell precursors. Journal of immunology 177: 2803–2809.

22. ZhangD, YangW, DegauqueN, TianY, MikitaA, et al. (2007) New differentiation pathway for double-negative regulatory T cells that regulates the magnitude of immune responses. Blood 109: 4071–4079.

23. FischerK, VoelklS, HeymannJ, PrzybylskiGK, MondalK, et al. (2005) Isolation and characterization of human antigen-specific TCR alpha beta+ CD4(−)CD8- double-negative regulatory T cells. Blood 105: 2828–2835.

24. ZhangZX, YangL, YoungKJ, DuTempleB, ZhangL (2000) Identification of a previously unknown antigen-specific regulatory T cell and its mechanism of suppression. Nature medicine 6: 782–789.

25. YoungKJ, KayLS, PhillipsMJ, ZhangL (2003) Antitumor activity mediated by double-negative T cells. Cancer Res 63: 8014–8021.

26. YoungKJ, YangL, PhillipsMJ, ZhangL (2002) Donor-lymphocyte infusion induces transplantation tolerance by activating systemic and graft-infiltrating double-negative regulatory T cells. Blood 100: 3408–3414.

27. LeeBP, MansfieldE, HsiehSC, Hernandez-BoussardT, ChenW, et al. (2005) Expression profiling of murine double-negative regulatory T cells suggest mechanisms for prolonged cardiac allograft survival. Journal of immunology 174: 4535–4544.

28. FordMS, ChenW, WongS, LiC, VanamaR, et al. (2007) Peptide-activated double-negative T cells can prevent autoimmune type-1 diabetes development. European journal of immunology 37: 2234–2241.

29. DuncanB, Nazarov-StoicaC, SurlsJ, KehlM, BonaC, et al. (2010) Double negative (CD3+ 4- 8-) TCR alphabeta splenic cells from young NOD mice provide long-lasting protection against type 1 diabetes. PLoS One 5: e11427.

30. HillhouseEE, LesageS (2013) A comprehensive review of the phenotype and function of antigen-specific immunoregulatory double negative T cells. Journal of autoimmunity 40: 58–65.

31. CowleySC, HamiltonE, FrelingerJA, SuJ, FormanJ, et al. (2005) CD4-CD8- T cells control intracellular bacterial infections both in vitro and in vivo. The Journal of experimental medicine 202: 309–319.

32. CowleySC, MeierovicsAI, FrelingerJA, IwakuraY, ElkinsKL (2010) Lung CD4-CD8- double-negative T cells are prominent producers of IL-17A and IFN-gamma during primary respiratory murine infection with Francisella tularensis live vaccine strain. Journal of immunology 184: 5791–5801.

33. MilushJM, MirKD, SundaravaradanV, GordonSN, EngramJ, et al. (2011) Lack of clinical AIDS in SIV-infected sooty mangabeys with significant CD4+ T cell loss is associated with double-negative T cells. The Journal of clinical investigation 121: 1102–1110.

34. VintonC, KlattNR, HarrisLD, BriantJA, Sanders-BeerBE, et al. (2011) CD4-like immunological function by CD4- T cells in multiple natural hosts of simian immunodeficiency virus. Journal of virology 85: 8702–8708.

35. RestrepoC, RallonNI, del RomeroJ, RodriguezC, Sempere-OrtellsJM, et al. (2013) HIV Gag-specific immune response mediated by double negative (CD3(+)CD4(−)CD8(−)) T cells in HIV-exposed seronegative individuals. Journal of medical virology 85: 200–209.

36. KemperC, AtkinsonJP (2007) T-cell regulation: with complements from innate immunity. Nature reviews Immunology 7: 9–18.

37. BaudinoL, SardiniA, RusevaMM, Fossati-JimackL, CookHT, et al. (2014) C3 opsonization regulates endocytic handling of apoptotic cells resulting in enhanced T-cell responses to cargo-derived antigens. Proceedings of the National Academy of Sciences of the United States of America 111: 1503–1508.

38. LiszewskiMK, KolevM, Le FriecG, LeungM, BertramPG, et al. (2013) Intracellular complement activation sustains T cell homeostasis and mediates effector differentiation. Immunity 39: 1143–1157.

39. GhannamA, FauquertJL, ThomasC, KemperC, DrouetC (2014) Human complement C3 deficiency: Th1 induction requires T cell-derived complement C3a and CD46 activation. Molecular immunology 58: 98–107.

40. MulemeHM, RegueraRM, BerardA, AzinwiR, JiaP, et al. (2009) Infection with arginase-deficient Leishmania major reveals a parasite number-dependent and cytokine-independent regulation of host cellular arginase activity and disease pathogenesis. Journal of immunology 183: 8068–8076.

41. LiuD, UzonnaJE (2010) The p110 delta isoform of phosphatidylinositol 3-kinase controls the quality of secondary anti-Leishmania immunity by regulating expansion and effector function of memory T cell subsets. Journal of immunology 184: 3098–3105.