Systemic Hematogenous Maintenance of Memory Inflation by MCMV Infection

English version České info

Herpesviruses persist for the life of the host and must be continuously controlled by a robust immune surveillance effort. In the case of the cytomegalovirus (CMV), this ongoing immune surveillance promotes the accumulation of CMV-specific T cells in a process known as “memory inflation”. We and others have proposed that the ability to induce memory inflation may be an important benefit of CMV-based vaccine vectors that persist within the host and continuously boost the immune response. However, it has been difficult to determine where T cells are encountering CMV in the body, leading to many unanswered questions about the maintenance of this remarkable response. Previous models proposed that T cells encountered viral antigen within lymph nodes and then migrated to other tissues to prevent CMV reactivation. However, we found that the majority of T cells stimulated by CMV were present in circulation, where they could be sustained without the input from T cells localized to lymph nodes. In fact, two of the defining features of memory inflation -⁠ inflated numbers and an effector phenotype -⁠ were restricted to cells that were exposed to the blood. Thus, we propose that memory inflation during CMV infection is largely the result of immune surveillance that occurs in circulation.

Vyšlo v časopise: Systemic Hematogenous Maintenance of Memory Inflation by MCMV Infection. PLoS Pathog 10(7): e32767. doi:10.1371/journal.ppat.1004233
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004233

Souhrn

Zdroje

1. KoffronA, HummelM, PattersonB, YanS, KaufmanD, et al. (1998) Cellular Localization of Latent Murine Cytomegalovirus. J Virol 72 : 95–103.

2. JarvisMA, NelsonJA (2002) Human cytomegalovirus persistence and latency in endothelial cells and macrophages. Curr Opin Microbiol 5 : 403–407.

3. JarvisMA, NelsonJA (2007) Human cytomegalovirus tropism for endothelial cells: not all endothelial cells are created equal. J Virol 81 : 2095–2101.

4. MercerJ, WileyC, SpectorD (1988) Pathogenesis of Murine Cytomegalovirus Infection: Identification of Infected Cells in the Spleen during Acute and Latent Infections. J Virol 62 : 987–997.

5. PomeroyC, HillerenP, JordanM (1991) Latent Murine Cytomegalovirus DNA in Splenic Stromal Cells of Mice. J Virol 65 : 3330–3334.

6. HendrixM, SalimansM, van BovenC, BruggemanC (1990) High prevalence of latently present cytomegalovirus in arterial walls of patients suffering from grade III atherosclerosis. Am J Pathol 136 : 23–28.

7. HendrixM, DormansP, KitslaarP, BosmanF, BruggemanC (1989) The presence of cytomegalovirus nucleic acids in arterial walls of atherosclerotic and nonatherosclerotic patients. Am J Pathol 134 : 1151–1157.

8. HendrixR, WagenaarM, SlobbeR, BruggemanC (1997) Widespread presence of cytomegalovirus DNA in tissues of healthy trauma victims. J Clin Pathol 50 : 59–63.

9. Kondo K, Mocarski ES (1995) Cytomegalovirus latency and latency-specific transcription in hematopoietic progenitors. Scand J Infect Dis Suppl 99 : 63–67.

10. ReevesM, SissonsP, SinclairJ (2005) Reactivation of human cytomegalovirus in dendritic cells. Discov Med 5 : 170–174.

11. KondoK, KaneshimaH, MocarskiE (1994) Human cytomegalovirus latent infection of granulocyte-macrophage progenitors. Proc Natl Acad Sci U S A 91 : 11879–11883.

12. KondoK, XuJ, MocarskiE (1996) Human cytomegalovirus latent gene expression in granulocyte-macrophage progenitors in culture and in seropositive individuals. Proc Natl Acad Sci U S A 93 : 11137–11142.

13. GoodrumF, ReevesM, SinclairJ, HighK, ShenkT (2007) Human cytomegalovirus sequences expressed in latently infected individuals promote a latent infection in vitro. Blood 110 : 937–945.

14. GoodrumFD, JordanCT, HighK, ShenkT (2002) Human cytomegalovirus gene expression during infection of primary hematopoietic progenitor cells: a model for latency. Proc Natl Acad Sci U S A 99 : 16255–16260.

15. Taylor-WiedemanJ, SissonsJ, BorysiewiczL, SinclairJ (1991) Monocytes are a major site of persistence of human cytomegalovirus in peripheral blood mononuclear cells. J Gen Virol 72 : 2059–2064.

16. Söderberg-NauclérC, FishK, NelsonJ (1997) Reactivation of latent human cytomegalovirus by allogeneic stimulation of blood cells from healthy donors. Cell 91 : 119–126.

17. PollockJ, PrestiR, PaetzoldS, VirginH (1997) Latent murine cytomegalovirus infection in macrophages. Virology 227 : 168–179.

18. GrzimekNK, DreisD, SchmalzS, ReddehaseMJ (2001) Random, asynchronous, and asymmetric transcriptional activity of enhancer-flanking major immediate-early genes ie1/3 and ie2 during murine cytomegalovirus latency in the lungs. J Virol 75 : 2692–2705.

19. KurzSK, ReddehaseMJ (1999) Patchwork pattern of transcriptional reactivation in the lungs indicates sequential checkpoints in the transition from murine cytomegalovirus latency to recurrence. J Virol 73 : 8612–8622.

20. PolicB, HengelH, KrmpoticA, TrgovcichJ, PaviI, et al. (1998) Hierarchical and Redundant Lymphocyte Subset Control Precludes Cytomegalovirus Replication during Latent Infection. J Exp Med 188 : 1047–1054.

21. CroughT, KhannaR (2009) Immunobiology of Human Cytomegalovirus: from Bench to Bedside. Clin Microbal Rev 22 : 76–98.

22. SimonCO, HoltappelsR, TervoHM, BohmV, DaubnerT, et al. (2006) CD8 T cells control cytomegalovirus latency by epitope-specific sensing of transcriptional reactivation. J Virol 80 : 10436–10456.

23. HoltappelsR, BohmV, PodlechJ, ReddehaseMJ (2008) CD8 T-cell-based immunotherapy of cytomegalovirus infection: "proof of concept" provided by the murine model. Med Microbiol Immunol 197 : 125–134.

24. WalterE, GreenbergP, GilbertM, FinchR, WatanabeK, et al. (1995) Reconstitution of cellular immunity against cytomegalovirus in recipients of allogeneic bone marrow by transfer of T-cell clones from the donor. N Engl J Med 333 : 1038–1044.

25. ReddehaseM, JonjićS, WeilandF, MutterW, KoszinowskiU (1988) Adoptive immunotherapy of murine cytomegalovirus adrenalitis in the immunocompromised host: CD4-helper-independent antiviral function of CD8-positive memory T lymphocytes derived from latently infected donors. J Virol 62 : 1061–1065.

26. RiddellS, WatanabeK, GoodrichJ, LiC, AghaM, et al. (1992) Restoration of viral immunity in immunodeficient humans by the adoptive transfer of T cell clones. Science 257 : 238–241.

27. KarrerU, SierroS, WagnerM, OxeniusA, HengelH, et al. (2003) Memory Inflation: Continuous Accumulation of Antiviral CD8+ T Cells Over Time. J Immunol 170 : 2022–2029.

28. MunksMW, ChoKS, PintoAK, SierroS, KlenermanP, et al. (2006) Four Distinct Patterns of Memory CD8 T Cell Responses to Chronic Murine Cytomegalovirus Infection. J Immunol 177 : 450–458.

29. HoltappelsR, Pahl-SeibertM-F, ThomasD, ReddehaseMJ (2000) Enrichment of Immediate-Early 1 (m123/pp89) Peptide-Specific CD8 T Cells in a Pulmonary CD62Llo Memory-Effector Cell Pool during Latent Murine Cytomegalovirus Infection of the Lungs. J Virol 74 : 11495–11503.

30. KomatsuH, SierroS, V. CueroA, KlenermanP (2003) Population analysis of antiviral T cell responses using MHC class I-peptide tetramers. Clin Exp Immunol 134 : 9–12.

31. HoltappelsR, ThomasD, PodlechJ, ReddehaseMJ (2002) Two Antigenic Peptides from Genes m123 and m164 of Murine Cytomegalovirus Quantitatively Dominate CD8 T-Cell Memory in the H-2d Haplotype. Journal of Virology 76 : 151–164.

32. SylwesterAW, MitchellBL, EdgarJB, TaorminaC, PelteC, et al. (2005) Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects. J Exp Med 202 : 673–685.

33. BolingerB, SimsS, O'HaraG, de LaraC, TchilianE, et al. (2013) A new model for CD8+ T cell memory inflation based upon a recombinant adenoviral vector. J Immunol 190 : 4162–4174.

34. LangA, BrienJD, Nikolich-ZugichJ (2009) Inflation and long-term maintenance of CD8 T cells responding to a latent herpesvirus depend upon establishment of latency and presence of viral antigens. J Immunol 183 : 8077–8087.

35. NorbeckO, IsaA, PohlmannC, BrolidenK, KasprowiczV, et al. (2005) Sustained CD8+ T-cell responses induced after acute parvovirus B19 infection in humans. J Virol 79 : 12117–12121.

36. SimmonsR, SharpC, LevineJ, BownessP, SimmondsP, et al. (2013) Evolution of CD8+ T cell responses after acute PARV4 infection. J Virol 87 : 3087–3096.

37. SimmonsR, SharpC, SimsS, KloverprisH, GoulderP, et al. (2011) High frequency, sustained T cell responses to PARV4 suggest viral persistence in vivo. J Infect Dis 203 : 1378–1387.

38. SwansonPA, PackCD, HadleyA, WangCR, StroynowskiI, et al. (2008) An MHC class Ib-restricted CD8 T cell response confers antiviral immunity. J Exp Med 205 : 1647–1657.

39. IsaA, KasprowiczV, NorbeckO, LoughryA, JefferyK, et al. (2005) Prolonged activation of virus-specific CD8+T cells after acute B19 infection. PLoS Med 2: e343.

40. KaechSM, TanJT, WherryEJ, KoniecznyBT, SurhCD, et al. (2003) Selective expression of the interleukin 7 receptor identifies effector CD8 T cells that give rise to long-lived memory cells. Nat Immunol 4 : 1191–1198.

41. SarkarS, KaliaV, HainingWN, KoniecznyBT, SubramaniamS, et al. (2008) Functional and genomic profiling of effector CD8 T cell subsets with distinct memory fates. J Exp Med 205 : 625–640.

42. SierroS, RothkopfR, KlenermanP (2005) Evolution of diverse antiviral CD8+ T cell populations after murine cytomegalovirus infection. Eur J Immunol 35 : 1113–1123.

43. SnyderCM, ChoKS, BonnettEL, van DommelenS, ShellamGR, et al. (2008) Memory inflation during chronic viral infection is maintained by continuous production of short-lived, functional T cells. Immunity 29 : 650–659.

44. MasopustD, HaS, VezysV, AhmedR (2006) Stimulation history dictates memory CD8 T cell phenotype: implications for prime-boost vaccination. J Immunol 177 : 831–839.

45. 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.

46. KrmpoticA, BubicI, PolicB, LucinP, JonjicS (2003) Pathogenesis of murine cytomegalovirus infection. Microb Infect 5 : 1263–1277.

47. HansenSG, FordJC, LewisMS, VenturaAB, HughesCM, et al. (2011) Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine. Nature 473 : 523–527.

48. XuG, SmithT, GreyF, HillAB (2013) Cytomegalovirus-based cancer vaccines expressing TRP2 induce rejection of melanoma in mice. Biochem Biophys Res Commun 437 : 287–291.

49. KlyushnenkovaEN, KouiavskaiaDV, ParkinsCJ, CaposioP, BottoS, et al. (2012) A cytomegalovirus-based vaccine expressing a single tumor-specific CD8+ T-cell epitope delays tumor growth in a murine model of prostate cancer. J Immunother 35 : 390–399.

50. SnyderCM, ChoKS, BonnettEL, AllanJE, HillAB (2011) Sustained CD8+ T cell memory inflation after infection with a single-cycle cytomegalovirus. PLoS Pathog 7: e1002295.

51. van LeeuwenEM, de BreeGJ, RemmerswaalEB, YongSL, TesselaarK, et al. (2005) IL-7 receptor alpha chain expression distinguishes functional subsets of virus-specific human CD8+ T cells. Blood 106 : 2091–2098.

52. TortiN, WaltonSM, BrockerT, RulickeT, OxeniusA (2011) Non-hematopoietic cells in lymph nodes drive memory CD8 T cell inflation during murine cytomegalovirus infection. PLoS Pathog 7: e1002313.

53. WallaceDL, MastersJE, De LaraCM, HensonSM, WorthA, et al. (2011) Human cytomegalovirus-specific CD8(+) T-cell expansions contain long-lived cells that retain functional capacity in both young and elderly subjects. Immunology 132 : 27–38.

54. SeckertCK, SchaderSI, EbertS, ThomasD, FreitagK, et al. (2011) Antigen-presenting cells of haematopoietic origin prime cytomegalovirus-specific CD8 T-cells but are not sufficient for driving memory inflation during viral latency. J Gen Virol 92 : 1994–2005.

55. ThomasAC, ForsterMR, BickerstaffAA, ZimmermanPD, WingBA, et al. (2010) Occult cytomegalovirus in vivarium-housed mice may influence transplant allograft acceptance. Transpl Immunol 23 : 86–91.

56. TurulaH, SmithCJ, GreyF, ZurbachKA, SnyderCM (2013) Competition between T cells maintains clonal dominance during memory inflation induced by MCMV. Eur J Immunol 43 : 1252–1263.

57. HsuKM, PrattJR, AkersWJ, AchilefuSI, YokoyamaWM (2009) Murine cytomegalovirus displays selective infection of cells within hours after systemic administration. J Gen Virol 90 : 33–43.

58. SeckertCK, RenzahoA, TervoHM, KrauseC, DeegenP, et al. (2009) Liver sinusoidal endothelial cells are a site of murine cytomegalovirus latency and reactivation. J Virol 83 : 8869–8884.

59. PinschewerD, OchsenbeinA, OdermattB, BrinkmannV, HengartnerH, et al. (2000) FTY720 immunosuppression impairs effector T cell peripheral homing without affecting induction, expansion, and memory. J Immunol 164 : 5761–5770.

60. LedgerwoodLG, LalG, ZhangN, GarinA, EssesSJ, et al. (2008) The sphingosine 1-phosphate receptor 1 causes tissue retention by inhibiting the entry of peripheral tissue T lymphocytes into afferent lymphatics. Nat Immunol 9 : 42–53.

61. BrinkmanCC, RouhaniSJ, SrinivasanN, EngelhardVH (2013) Peripheral tissue homing receptors enable T cell entry into lymph nodes and affect the anatomical distribution of memory cells. J Immunol 191 : 2412–2425.

62. AndersonKG, SungH, SkonCN, LefrancoisL, DeisingerA, et al. (2012) Cutting edge: intravascular staining redefines lung CD8 T cell responses. J Immunol 189 : 2702–2706.

63. GalkinaE, ThatteJ, DabakV, WilliamsMB, LeyK, et al. (2005) Preferential migration of effector CD8+ T cells into the interstitium of the normal lung. J Clin Invest 115 : 3473–3483.

64. AndersonKG, Mayer-BarberK, SungH, BeuraL, JamesBR, et al. (2014) Intravascular staining for discrimination of vascular and tissue leukocytes. Nat Protoc 9 : 209–222.

65. HertoghsK, MoerlandP, van StijnA, RemmerswaalE, YongS, et al. (2010) Molecular profiling of cytomegalovirus-induced human CD8+ T cell differentiation. J Clin Invest 120 : 4077–4090.

66. PodlechJ, HoltappelsR, Pahl-SeibertM-F, SteffensH-P, ReddehaseMJ (2000) Murine Model of Interstitial Cytomegalovirus Pneumonia in Syngeneic Bone Marrow Transplantation: Persistence of Protective Pulmonary CD8-T-Cell Infiltrates after Clearance of Acute Infection. J Virol 74 : 7496–7507.

67. KurzSK, RappM, SteffensH-P, GrzimekNKA, SchmalzS, et al. (1999) Focal Transcriptional Activity of Murine Cytomegalovirus during Latency in the Lungs. J Virol 73 : 482–494.

68. MatloubianM, LoC, CinamonG, LesneskiM, XuY, et al. (2004) Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1. Nature 427 : 355–360.

69. ArnonTI, CysterJG (2014) Blood, sphingosine-1-phosphate and lymphocyte migration dynamics in the spleen. Curr Top Microbiol Immunol 378 : 107–128.

70. Oliver P, Heike H, Stefanie W, Tim W, Angela S, et al.. (2006) Enhanced FTY720-Mediated Lymphocyte Homing Requires Gαi Signaling and Depends on β2 and β7 Integrin. J Immunol: 1474–1480.

71. FarringtonLA, SmithTA, GreyF, HillAB, SnyderCM (2013) Competition for antigen at the level of the APC is a major determinant of immunodominance during memory inflation in murine cytomegalovirus infection. J Immunol 190 : 3410–3416.

72. KernM, PopovA, ScholzK, SchumakB, DjandjiD, et al. (2010) Virally infected mouse liver endothelial cells trigger CD8+ T-cell immunity. Gastroenterology 138 : 336–346.

73. WarrenA, Le CouteurDG, FraserR, BowenDG, McCaughanGW, et al. (2006) T lymphocytes interact with hepatocytes through fenestrations in murine liver sinusoidal endothelial cells. Hepatology 44 : 1182–1190.

74. HummelM, ZhangZ, YanS, DePlaenI, GoliaP, et al. (2001) Allogeneic transplantation induces expression of cytomegalovirus immediate-early genes in vivo: a model for reactivation from latency. J Virol 75 : 4814–4822.

75. van de BergPJ, YongSL, RemmerswaalEB, van LierRA, ten BergeIJ (2012) Cytomegalovirus-induced effector T cells cause endothelial cell damage. Clin Vaccine Immunol 19 : 772–779.

76. LangA, Nikolich-ZugichJ (2011) Functional CD8 T cell memory responding to persistent latent infection is maintained for life. J Immunol 187 : 3759–3768.

77. HutchinsonS, SimsS, O'HaraG, SilkJ, GileadiU, et al. (2011) A dominant role for the immunoproteasome in CD8+ T cell responses to murine cytomegalovirus. PLoS One 6: e14646.

78. HoltappelsR, PodlechJ, Pahl-SeibertMF, JulchM, ThomasD, et al. (2004) Cytomegalovirus misleads its host by priming of CD8 T cells specific for an epitope not presented in infected tissues. J Exp Med 199 : 131–136.

79. JungYW, RutishauserRL, JoshiNS, HabermanAM, KaechSM (2010) Differential localization of effector and memory CD8 T cell subsets in lymphoid organs during acute viral infection. J Immunol 185 : 5315–5325.

80. RemmerswaalEB, HavenithSH, IduMM, van LeeuwenEM, van DonselaarKA, et al. (2012) Human virus-specific effector-type T cells accumulate in blood but not in lymph nodes. Blood 119 : 1702–1712.

81. ZurbachKA, MoghbeliT, SnyderCM (2014) Resolving the titer of murine cytomegalovirus by plaque assay using the M2-10B4 cell line and low viscosity overlay. Virology Journal 11 : 71.

82. ZhangJ, DongZ, ZhouR, LuoD, WeiH, et al. (2005) Isolation of Lymphocytes and Their Innate Immune Characterizations from Liver, Intestine, Lung and Uterus. Cell Mol Immunol 2 : 271–280.

83. MegaJ, McGheeJ, KiyonoH (1992) Cytokine -⁠ and Ig-producing T cells in mucosal effector tissues: analysis of IL-5 -⁠ and IFN-gamma-producing T cells, T cell receptor expression, and IgA plasma cells from mouse salivary gland-associated tissues. J Immunol 148 : 2030–2038.