1887

Abstract

The role that T cell subsets play in herpetic stromal keratitis (HSK) has been the subject of intense research efforts. While most studies implicate CD4 T cells as the principal cell type mediating primary corneal disease, recent reports using knockout mice have suggested that both CD4 and CD8 T cell subsets may play integral roles in modulating the disease. Furthermore, recent studies suggest that CD8 T cells are directly involved in maintaining virus latency in infected trigeminal ganglia. This work has addressed these discrepancies by infecting the corneas of mice lacking CD4 and CD8 T cells with herpes simplex virus type 1 (HSV-1) and monitoring both corneal disease and latent infection of trigeminal ganglia. Results indicated that mice lacking CD8 T cells had more severe corneal disease than either BALB/c or B6 parental strains. In contrast, mice lacking CD4 T cells had a milder disease than parental strains. When mice were evaluated for persistence of infectious virus, only transient differences were observed in periocular tissue and corneas. No significant differences were found in persistence of virus in trigeminal ganglia or virus reactivation from explanted ganglia. These data support the following conclusions. CD4 T cells are not required for resistance to infection with HSV-1 and probably mediate HSK. Mice lacking CD8 T cells do not display differences in viral loads or reactivation and thus CD8 T cells are not absolutely required to maintain latency. Finally, CD8 T cells probably play a protective role by regulating the immunopathological response that mediates HSK.

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2004-07-01
2024-03-29
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References

  1. Akova Y. A., Dutt J., Rodriguez A., Jabbur N., Foster C. S. 1993; The role of Igh-1 disparate congenic mouse T lymphocytes in the pathogenesis of herpetic stromal keratitis. Curr Eye Res 12:1093–1101 [CrossRef]
    [Google Scholar]
  2. Chan W. L., Lukig M. L., Liew F. Y. 1985; Helper T cells induced by an immunopurified herpes simplex virus type I (HSV-I) 115 kilodalton glycoprotein (gB) protect mice against HSV-I infection. J Exp Med 162:1304–1318 [CrossRef]
    [Google Scholar]
  3. Cortesini R., Renna-Molajoni E., Cinti P., Pretagostini R., Ho E., Rossi P., Suciu-Foca Cortesini N. 2002; Tailoring of immunosuppression in renal and liver allograft recipients displaying donor specific T-suppressor cells. Hum Immunol 63:1010–1018 [CrossRef]
    [Google Scholar]
  4. Cosmi L., Liotta F., Lazzeri E. 10 other authors 2003; Human CD8+CD25+ thymocytes sharing phenotypic and functional features with CD4+CD25+ regulatory thymocytes. Blood 102:4107–4114 [CrossRef]
    [Google Scholar]
  5. Doymaz M. Z., Rouse B. T. 1992; Herpetic stromal keratitis: an immunopathologic disease mediated by CD4+ T lymphocytes. Invest Ophthalmol Vis Sci 33:2165–2173
    [Google Scholar]
  6. Ferguson T. A., Herndon J., Elzey B., Griffith T. S., Schoenberger S., Green D. R. 2002; Uptake of apoptotic antigen-coupled cells by lymphoid dendritic cells and cross-priming of CD8+ T cells produce active immune unresponsiveness. J Immunol 168:5589–5595 [CrossRef]
    [Google Scholar]
  7. Ferguson T. A., Stuart P. M., Herndon J. M., Griffith T. S. 2003; Apoptosis, tolerance and regulatory T cells. Old wine, new wineskins. Immunol Rev 193:111–123 [CrossRef]
    [Google Scholar]
  8. Field E. H., Matesic D., Rigby S., Fehr T., Rouse T., Gao Q. 2001; CD4+CD25+ regulatory cells in acquired MHC tolerance. Immunol Rev 182:99–112 [CrossRef]
    [Google Scholar]
  9. Filaci G., Suciu-Foca N. 2002; CD8+ T suppressor cells are back to the game: are they players in autoimmunity?. Autoimmun Rev 1:279–283 [CrossRef]
    [Google Scholar]
  10. Geiss B. J., Smith T. J., Leib D. A., Morrison L. A. 2000; Disruption of virion host shutoff activity improves the immunogenicity and protective capacity of a replication-incompetent herpes simplex virus type 1 vaccine strain. J Virol 74:11137–11144 [CrossRef]
    [Google Scholar]
  11. Ghiasi H., Cai S., Nesburn A. B., Wechsler S. L. 1997; MHC-II but not MHC-I responses are required for vaccine-induced protection against ocular challenge with HSV-1. Curr Eye Res 16:1152–1158 [CrossRef]
    [Google Scholar]
  12. Ghiasi H., Perng G.-Y., Nesburn A. B., Wechsler S. L. 1999; Either CD4+ or CD8+ T cell function is sufficient for clearance of infectious virus from trigeminal ganglia and establishment of herpes simplex virus type 1 latency in mice. Microb Pathog 27:387–394 [CrossRef]
    [Google Scholar]
  13. Ghiasi H., Cai S., Perng G.-Y., Nesburn A. B., Wechsler S. L. 2000; Both CD4+ and CD8+ T cells are involved in protection against HSV-1 induced corneal scarring. Br J Ophthalmol 84:408–412 [CrossRef]
    [Google Scholar]
  14. Gilliet M., Liu Y. J. 2002a; Generation of human CD8 T regulatory cells by CD40 ligand-activated plasmacytoid dendritic cells. J Exp Med 195:695–704 [CrossRef]
    [Google Scholar]
  15. Gilliet M., Liu Y. J. 2002b; Human plasmacytoid-derived dendritic cells and the induction of T-regulatory cells. Hum Immunol 63:1149–1155 [CrossRef]
    [Google Scholar]
  16. Hafalla J. C., Morrot A., Sano G., Milon G., Lafaille J. J., Zavala F. 2003; Early self-regulatory mechanisms control the magnitude of CD8+ T cell responses against liver stages of murine malaria. J Immunol 171:964–970 [CrossRef]
    [Google Scholar]
  17. Haskova Z., Usui N., Ferguson T. A., Pepose J. S., Stuart P. M. 2000; CD4+ T cells are critical in corneal but not skin allograft rejection. Transplantation 69:483–488 [CrossRef]
    [Google Scholar]
  18. Hendricks R. L., Tumpey T. M. 1990; Contribution of virus and immune factors to herpes simplex virus type 1-induced corneal pathology. Invest Ophthalmol Vis Sci 31:1929–1939
    [Google Scholar]
  19. Irie H., Aita K., Koyama A. H., Fukuda A., Yoshida T., Shiga J. 2002; The role of donor CD4+ T cells in the reconstitution of oral immunity by herpes simplex virus type 1 in severe combined immunodeficiency mice. J Infect Dis 185:409–416 [CrossRef]
    [Google Scholar]
  20. Jiang H., Chess L. 2000; The specific regulation of immune responses by CD8+ T cells restricted by the MHC class Ib molecule, Qa-1. Annu Rev Immunol 18:185–216 [CrossRef]
    [Google Scholar]
  21. Jiang H., Braunstein N. S., Yu B., Winchester R., Chess L. 2001; CD8+ T cells control the TH phenotype of MBP-reactive CD4+ T cells in EAE mice. Proc Natl Acad Sci U S A 98:6301–6306 [CrossRef]
    [Google Scholar]
  22. Keadle T. L., Morris J. L., Pepose J. S., Stuart P. M. 2002a; CD4+ and CD8+ cells are key participants in the development of recurrent herpetic stromal keratitis in mice. Microb Pathog 32:255–262 [CrossRef]
    [Google Scholar]
  23. Keadle T. L., Morrison L. A., Morris J., Pepose J. S., Stuart P. M. 2002b; Therapeutic immunization with a virion host shutoff ( vhs ) defective, replication-incompetent HSV-1 strain limits recurrent herpetic ocular infection. J Virol 76:3615–3625 [CrossRef]
    [Google Scholar]
  24. Kennedy P. G., Lisak R. P., Raff M. C. 1980; Cell type-specific markers for human glial and neuronal cells in culture. Lab Invest 43:342–351
    [Google Scholar]
  25. Khanna K. M., Bonneau R. H., Kinchington P. R., Hendricks R. L. 2003; Herpes simplex virus-specific memory CD8+ T cells are selectively activated and retained in latently infected sensory ganglia. Immunity 18:593–603 [CrossRef]
    [Google Scholar]
  26. Koelle D. M., Reymond S. N., Chen H. 7 other authors 2000; Tegument-specific, virus-reactive CD4 T cells localize to the cornea in herpes simplex virus interstitial keratitis in humans. J Virol 74:10930–10938 [CrossRef]
    [Google Scholar]
  27. Liu T., Khanna K. M., Chen X., Fink D. J., Hendricks R. L. 2000; CD8+ T cells can block herpes simplex virus type 1 (HSV-1) reactivation from latency in sensory neurons. J Exp Med 191:1459–1466 [CrossRef]
    [Google Scholar]
  28. Liu T., Khanna K. M., Carriere B. N., Hendricks R. L. 2001; Gamma interferon can prevent herpes simplex virus type 1 reactivation from latency in sensory neurons. J Virol 75:11178–11184 [CrossRef]
    [Google Scholar]
  29. Maertzdorf J., Verjans G. M., Remeijer L., van der Kooi A., Osterhaus A. D. 2003; Restricted T cell receptor beta-chain variable region protein use by cornea-derived CD4+ and CD8+ herpes simplex virus-specific T cells in patients with herpetic stromal keratitis. J Infect Dis 187:550–558 [CrossRef]
    [Google Scholar]
  30. Metcalf J. F., Hamilton D. S., Reichert R. W. 1979; Herpetic keratitis in athymic (nude) mice. Infect Immun 26:1164–1171
    [Google Scholar]
  31. Miller J. K., Laycock K. A., Umphress J. A., Hook K. K., Stuart P. M., Pepose J. S. 1996; A comparison of recurrent versus primary HSK in inbred mice. Cornea 15:497–504
    [Google Scholar]
  32. Morrison L. A., Knipe D. M. 1997; Contributions of antibody and T cell subsets to protection elicited by immunization with a replication-defective mutant of herpes simplex virus type 1. Virology 239:315–326 [CrossRef]
    [Google Scholar]
  33. Nakamura T., Sonoda K. H., Faunce D. E., Gumperz J., Yamamura T., Miyake S., Stein-Streilein J. 2003; CD4+ NKT cells, but not conventional CD4+ T cells, are required to generate efferent CD8+ T regulatory cells following antigen inoculation in an immune-privileged site. J Immunol 171:1266–1271 [CrossRef]
    [Google Scholar]
  34. Newell C. K., Martin S., Sendele D., Mercadal C. M., Rouse B. T. 1989; Herpes simplex virus-induced stromal keratitis: role of T-lymphocyte subsets in immunopathology. J Virol 63:769–775
    [Google Scholar]
  35. Nicholson S. M., Dal Canto M. C., Miller S. D., Melvold R. W. 1996; Adoptively transferred CD8+ T lymphocytes against TMEV-induced demyelinating disease in BALB/c mice. J Immunol 156:1276–1283
    [Google Scholar]
  36. Niemialtowski M. G., Rouse B. T. 1992; Phenotype and functional studies on ocular T cells during herpetic infections of the eye. J Immunol 148:1864–1870
    [Google Scholar]
  37. Pepose J. S., Leib D. A., Stuart P. M., Easty E. L. 1996; Herpes simplex virus diseases: anterior segment of the eye. In Ocular Infection and Immunity pp  905–932 Edited by Pepose J. S., Holland G. A. N., Wilhelmus K. R. St Louis, MO: Mosby;
    [Google Scholar]
  38. Piccirillo C. A., Shevach E. M. 2001; Cutting edge: control of CD8+ T cell activation by CD4+CD25+ immunoregulatory cells. J Immunol 167:1137–1140 [CrossRef]
    [Google Scholar]
  39. Rader K. A., Ackland-Berglund C. E., Miller J. K., Pepose J. S., Leib D. A. 1993; In vivo characterization of site-directed mutations in the promoter of the herpes simplex virus type 1 latency-associated transcripts. J Gen Virol 74:1859–1869 [CrossRef]
    [Google Scholar]
  40. Russell R. G., Nasisse M. P., Larsen H. S., Rouse B. T. 1984; Role of T-lymphocytes in the pathogenesis of herpetic stromal keratitis. Invest Ophthalmol Vis Sci 25:938–944
    [Google Scholar]
  41. Shevach E. M. 2000; Regulatory T cells in autoimmmunity. Annu Rev Immunol 18:423–449 [CrossRef]
    [Google Scholar]
  42. Shimeld C., Hill T. J., Blyth W. A., Easty D. L. 1990; Passive immunization protects the mouse eye from damage after herpes simplex virus infection by limiting spread of virus in the nervous system. J Gen Virol 71:681–687 [CrossRef]
    [Google Scholar]
  43. Skelsey M. E., Mayhew E., Niederkorn J. Y. 2003; CD25+, interleukin-10-producing CD4+ T cells are required for suppressor cell production and immune privilege in the anterior chamber of the eye. Immunology 110:18–29 [CrossRef]
    [Google Scholar]
  44. Smith T. J., Ackland-Berglund C. E., Leib D. A. 2000; Herpes simplex virus virion host shutoff ( vhs ) activity alters periocular disease in mice. J Virol 74:3598–3604 [CrossRef]
    [Google Scholar]
  45. Stuart P. M., Pan F., Plambeck S., Ferguson T. A. 2003; FasL–Fas ligand interactions regulate neovascularization in the cornea. Invest Ophthalmol Vis Sci 44:93–98 [CrossRef]
    [Google Scholar]
  46. Suvas S., Kumaraguru U., Pack C. D., Lee S., Rouse B. T. 2003; CD4+CD25+ T cells regulate virus-specific primary and memory CD8+ T cell responses. J Exp Med 198:889–901 [CrossRef]
    [Google Scholar]
  47. Taneja V., Taneja N., Paisansinsup T., Behrens M., Griffiths M., Luthra H., David C. S. 2002; CD4 and CD8 T cells in susceptibility/protection to collagen-induced arthritis in HLA-DQ8-transgenic mice: implications for rheumatoid arthritis. J Immunol 168:5867–5875 [CrossRef]
    [Google Scholar]
  48. Thomas J., Rouse B. T. 1997; Immunopathogenesis of herpetic ocular disease. Immunol Res 16:375–386 [CrossRef]
    [Google Scholar]
  49. Verjans G. M., Remeijer L., van Binnendijk R. S., Cornelissen J. G., Volker-Dieben J. H., Baarsma S. G., Osterhaus A. D. 1998; Identification and characterization of herpes simplex virus-specific CD4+ T cells in corneas of herpetic stromal keratitis patients. J Infect Dis 177:484–488 [CrossRef]
    [Google Scholar]
  50. Youinou P., Colin J., Mottier D. 1985; Immunological analysis of the cornea in herpetic stromal keratitis. J Clin Lab Immunol 17:105–106
    [Google Scholar]
  51. Youinou P., Colin J., Ferec C. 1986; Monoclonal antibody analysis of blood and cornea T lymphocyte subpopulations in herpes simplex keratitis. Graefes Arch Clin Exp Ophthalmol 224:131–133 [CrossRef]
    [Google Scholar]
  52. Zhang X., Jiang S., Manczak M., Sugden B., Adamus G. 2002; Phenotypes of T cells infiltrating the eyes in autoimmune anterior uveitis associated with EAE. Invest Ophthalmol Vis Sci 43:1499–1508
    [Google Scholar]
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