Infection of Adult Thymus with Murine Retrovirus Induces Virus-Specific Central Tolerance That Prevents Functional Memory CD8 T Cell Differentiation

English version České info

During thymocyte development, cells that recognize self-antigens are specifically deleted by the process known as negative selection. However, some pathogens disseminate to the thymus, and can induce foreign antigen presentation within this organ, resulting in potentially harmful clonal deletion of pathogen-specific T-lymphocyte precursors. In chronic infections, pathogen-specific T cells in the periphery progressively lose their functionality due to continual stimulation with the persisting antigen, a phenomenon known as T cell exhaustion. However, pathogen-reactive naïve T cells freshly primed during the chronic phase of infection can nevertheless replenish the functional pool of memory T cells. Therefore, a lack of their generation in the face of peripheral exhaustion may ultimately cause the loss of functional memory T cells and the resultant lack of pathogen control. In this study, we demonstrate that Friend murine retrovirus can utilize the above immune evasion strategy, a combination of ongoing peripheral exhaustion and virus-induced central tolerance. Our data suggest that, along with the reinvigoration of exhausted T cells in the periphery, preservation of the thymic function in supplying pathogen-specific naïve T cells may be important when considering immunological control of chronic infection with thymotropic pathogens.

Vyšlo v časopise: Infection of Adult Thymus with Murine Retrovirus Induces Virus-Specific Central Tolerance That Prevents Functional Memory CD8 T Cell Differentiation. PLoS Pathog 10(3): e32767. doi:10.1371/journal.ppat.1003937
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1003937

Souhrn

Zdroje

1. KaechSM, CuiW (2012) Transcriptional control of effector and memory CD8(+) T cell differentiation. Nat Rev Immunol 12: 749–761.

2. WherryEJ (2011) T cell exhaustion. Nat Immunol 12: 492–499.

3. BlackburnSD, ShinH, HainingWN, ZouT, WorkmanCJ, et al. (2009) Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat Immunol 10: 29–37.

4. ShinH, BlackburnSD, BlattmanJN, WherryEJ (2007) Viral antigen and extensive division maintain virus-specific CD8 T cells during chronic infection. J Exp Med 204: 941–949.

5. VezysV, MasopustD, KemballCC, BarberDL, O'MaraLA, et al. (2006) Continuous recruitment of naive T cells contributes to heterogeneity of antiviral CD8 T cells during persistent infection. J Exp Med 203: 2263–2269.

6. WilsonJJ, PackCD, LinE, FrostEL, AlbrechtJA, et al. (2012) CD8 T cells recruited early in mouse polyomavirus infection undergo exhaustion. J Immunol 188: 4340–4348.

7. D'SouzaWN, HedrickSM (2006) Cutting edge: latecomer CD8 T cells are imprinted with a unique differentiation program. J Immunol 177: 777–781.

8. MiyazawaM, Tsuji-KawaharaS, KanariY (2008) Host genetic factors that control immune responses to retrovirus infections. Vaccine 26: 2981–2996.

9. KimJW, ClossEI, AlbrittonLM, CunninghamJM (1991) Transport of cationic amino acids by the mouse ecotropic retrovirus receptor. Nature 352: 725–728.

10. WangH, KavanaughMP, NorthRA, KabatD (1991) Cell-surface receptor for ecotropic murine retroviruses is a basic amino-acid transporter. Nature 352: 729–731.

11. LiJP, D'AndreaAD, LodishHF, BaltimoreD (1990) Activation of cell growth by binding of Friend spleen focus-forming virus gp55 glycoprotein to the erythropoietin receptor. Nature 343: 762–764.

12. PersonsDA, PaulsonRF, LoydMR, HerleyMT, BodnerSM, et al. (1999) Fv2 encodes a truncated form of the Stk receptor tyrosine kinase. Nat Genet 23: 159–165.

13. ChesebroB, BloomM, WehrlyK, NishioJ (1979) Persistence of infectious Friend virus in spleens of mice after spontaneous recovery from virus-induced erythroleukemia. J Virol 32: 832–837.

14. DittmerU, HeH, MesserRJ, SchimmerS, OlbrichAR, et al. (2004) Functional impairment of CD8(+) T cells by regulatory T cells during persistent retroviral infection. Immunity 20: 293–303.

15. ZelinskyyG, DietzeKK, HuseckenYP, SchimmerS, NairS, et al. (2009) The regulatory T-cell response during acute retroviral infection is locally defined and controls the magnitude and duration of the virus-specific cytotoxic T-cell response. Blood 114: 3199–3207.

16. ZelinskyyG, KraftAR, SchimmerS, ArndtT, DittmerU (2006) Kinetics of CD8+ effector T cell responses and induced CD4+ regulatory T cell responses during Friend retrovirus infection. Eur J Immunol 36: 2658–2670.

17. RobertsonSJ, MesserRJ, CarmodyAB, HasenkrugKJ (2006) In vitro suppression of CD8+ T cell function by Friend virus-induced regulatory T cells. J Immunol 176: 3342–3349.

18. MyersL, MesserRJ, CarmodyAB, HasenkrugKJ (2009) Tissue-specific abundance of regulatory T cells correlates with CD8+ T cell dysfunction and chronic retrovirus loads. J Immunol 183: 1636–1643.

19. IwashiroM, MesserRJ, PetersonKE, StromnesIM, SugieT, et al. (2001) Immunosuppression by CD4+ regulatory T cells induced by chronic retroviral infection. Proc Natl Acad Sci U S A 98: 9226–9230.

20. DietzeKK, ZelinskyyG, GibbertK, SchimmerS, FrancoisS, et al. (2011) Transient depletion of regulatory T cells in transgenic mice reactivates virus-specific CD8+ T cells and reduces chronic retroviral set points. Proc Natl Acad Sci U S A 108: 2420–2425.

21. TakamuraS, Tsuji-KawaharaS, YagitaH, AkibaH, SakamotoM, et al. (2010) Premature terminal exhaustion of Friend virus-specific effector CD8+ T cells by rapid induction of multiple inhibitory receptors. J Immunol 184: 4696–4707.

22. NittaT, OhigashiI, TakahamaY (2013) The development of T lymphocytes in fetal thymus organ culture. Methods Mol Biol 946: 85–102.

23. BoursalianTE, GolobJ, SoperDM, CooperCJ, FinkPJ (2004) Continued maturation of thymic emigrants in the periphery. Nat Immunol 5: 418–425.

24. MakaroffLE, HendricksDW, NiecRE, FinkPJ (2009) Postthymic maturation influences the CD8 T cell response to antigen. Proc Natl Acad Sci U S A 106: 4799–4804.

25. WherryEJ, BlattmanJN, Murali-KrishnaK, van der MostR, AhmedR (2003) Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment. J Virol 77: 4911–4927.

26. SrinivasanM, FrauwirthKA (2009) Peripheral tolerance in CD8+ T cells. Cytokine 46: 147–159.

27. YoungGR, PloquinMJ, EksmondU, WadwaM, StoyeJP, et al. (2012) Negative selection by an endogenous retrovirus promotes a higher-avidity CD4+ T cell response to retroviral infection. PLoS Pathog 8: e1002709.

28. GaultonGN (1998) Viral pathogenesis and immunity within the thymus. Immunol Res 17: 75–82.

29. CollavoD, ZanovelloP, BiasiG, Chieco-BianchiL (1981) T lymphocyte tolerance and early appearance of virus-induced cell surface antigens in Moloney-murine leukemia virus neonatally injected mice. J Immunol 126: 187–193.

30. Finke D, Acha-Orbea H (2001) Immune response to murine and feline retroviruses; Pantaleo G, Walker BD, editors. New Jersey: Humana Press, Inc. 125–157 p.

31. ZanovelloP, CollavoD, RoncheseF, De RossiA, BiasiG, et al. (1984) Virus-specific T cell response prevents lymphoma development in mice infected by intrathymic inoculation of Moloney leukaemia virus (M-MuLV). Immunology 51: 9–16.

32. MarshallDJ, ParkBH, KorostoffJM, GaultonGN (1995) Manipulation of the immune response by foreign gene expression in the thymus. Leukemia 9 Suppl 1: S128–132.

33. JamiesonBD, SomasundaramT, AhmedR (1991) Abrogation of tolerance to a chronic viral infection. J Immunol 147: 3521–3529.

34. KingCC, JamiesonBD, ReddyK, BaliN, ConcepcionRJ, et al. (1992) Viral infection of the thymus. J Virol 66: 3155–3160.

35. ZajacAJ, BlattmanJN, Murali-KrishnaK, SourdiveDJ, SureshM, et al. (1998) Viral immune evasion due to persistence of activated T cells without effector function. J Exp Med 188: 2205–2213.

36. NobregaC, RoqueS, Nunes-AlvesC, CoelhoA, MedeirosI, et al. (2010) Dissemination of mycobacteria to the thymus renders newly generated T cells tolerant to the invading pathogen. J Immunol 184: 351–358.

37. NobregaC, CardonaPJ, RoqueS, Pinto doOP, AppelbergR, et al. (2007) The thymus as a target for mycobacterial infections. Microbes Infect 9: 1521–1529.

38. MillerNE, BonczykJR, NakayamaY, SureshM (2005) Role of thymic output in regulating CD8 T-cell homeostasis during acute and chronic viral infection. J Virol 79: 9419–9429.

39. EdelmannSL, MarconiP, BrockerT (2011) Peripheral T cells re-enter the thymus and interfere with central tolerance induction. J Immunol 186: 5612–5619.

40. HadeibaH, LahlK, EdalatiA, OderupC, HabtezionA, et al. (2012) Plasmacytoid dendritic cells transport peripheral antigens to the thymus to promote central tolerance. Immunity 36: 438–450.

41. BonasioR, ScimoneML, SchaerliP, GrabieN, LichtmanAH, et al. (2006) Clonal deletion of thymocytes by circulating dendritic cells homing to the thymus. Nat Immunol 7: 1092–1100.

42. VogelAB, HaasbachE, ReilingSJ, DroebnerK, KlingelK, et al. (2010) Highly pathogenic influenza virus infection of the thymus interferes with T lymphocyte development. J Immunol 185: 4824–4834.

43. RobertsonMN, MiyazawaM, MoriS, CaugheyB, EvansLH, et al. (1991) Production of monoclonal antibodies reactive with a denatured form of the Friend murine leukemia virus gp70 envelope protein: use in a focal infectivity assay, immunohistochemical studies, electron microscopy and western blotting. J Virol Methods 34: 255–271.

44. LynchWP, CzubS, McAteeFJ, HayesSF, PortisJL (1991) Murine retrovirus-induced spongiform encephalopathy: productive infection of microglia and cerebellar neurons in accelerated CNS disease. Neuron 7: 365–379.

45. JordanMS, BoesteanuA, ReedAJ, PetroneAL, HolenbeckAE, et al. (2001) Thymic selection of CD4+CD25+ regulatory T cells induced by an agonist self-peptide. Nat Immunol 2: 301–306.

46. MaloyKJ, PowrieF (2001) Regulatory T cells in the control of immune pathology. Nat Immunol 2: 816–822.

47. MarodonG, FissonS, LevacherB, FabreM, SalomonBL, et al. (2006) Induction of antigen-specific tolerance by intrathymic injection of lentiviral vectors. Blood 108: 2972–2978.

48. MyersL, JoedickeJJ, CarmodyAB, MesserRJ, KassiotisG, et al. (2013) IL-2-independent and TNF-alpha-dependent expansion of Vbeta5+ natural regulatory T cells during retrovirus infection. J Immunol 190: 5485–5495.

49. AntunesI, TolainiM, KissenpfennigA, IwashiroM, KuribayashiK, et al. (2008) Retrovirus-specificity of regulatory T cells is neither present nor required in preventing retrovirus-induced bone marrow immune pathology. Immunity 29: 782–794.

50. HazraR, MackallC (2005) Thymic function in HIV infection. Curr HIV/AIDS Rep 2: 24–28.

51. TakedaE, Tsuji-KawaharaS, SakamotoM, LangloisMA, NeubergerMS, et al. (2008) Mouse APOBEC3 restricts friend leukemia virus infection and pathogenesis in vivo. J Virol 82: 10998–11008.

52. HogquistKA, JamesonSC, HeathWR, HowardJL, BevanMJ, et al. (1994) T cell receptor antagonist peptides induce positive selection. Cell 76: 17–27.

53. KuwataN, IgarashiH, OhmuraT, AizawaS, SakaguchiN (1999) Cutting edge: absence of expression of RAG1 in peritoneal B-1 cells detected by knocking into RAG1 locus with green fluorescent protein gene. J Immunol 163: 6355–6359.

54. ChesebroB, BrittW, EvansL, WehrlyK, NishioJ, et al. (1983) Characterization of monoclonal antibodies reactive with murine leukemia viruses: use in analysis of strains of friend MCF and Friend ecotropic murine leukemia virus. Virology 127: 134–148.

55. Tsuji-KawaharaS, ChikaishiT, TakedaE, KatoM, KinoshitaS, et al. (2010) Persistence of viremia and production of neutralizing antibodies differentially regulated by polymorphic APOBEC3 and BAFF-R loci in friend virus-infected mice. J Virol 84: 6082–6095.

56. Van VlietE, MelisM, Van EwijkW (1984) Monoclonal antibodies to stromal cell types of the mouse thymus. Eur J Immunol 14: 524–529.

57. McAteeFJ, PortisJL (1985) Monoclonal antibodies specific for wild mouse neurotropic retrovirus: detection of comparable levels of virus replication in mouse strains susceptible and resistant to paralytic disease. J Virol 56: 1018–1022.

58. OgawaT, Tsuji-KawaharaS, YuasaT, KinoshitaS, ChikaishiT, et al. (2011) Natural killer cells recognize friend retrovirus-infected erythroid progenitor cells through NKG2D-RAE-1 interactions In Vivo. J Virol 85: 5423–5435.

59. Tsuji-KawaharaS, KawabataH, MatsukumaH, KinoshitaS, ChikaishiT, et al. (2013) Differential requirements of cellular and humoral immune responses for fv2-associated resistance to erythroleukemia and for regulation of retrovirus-induced myeloid leukemia development. J Virol 87: 13760–13774.

60. YangC, CompansRW (1997) Analysis of the murine leukemia virus R peptide: delineation of the molecular determinants which are important for its fusion inhibition activity. J Virol 71: 8490–8496.