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Histological and immunopathological analysis of T-cells mediating murine HSV-1 keratitis

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Abstract

• Background: Thymusderived lymphocytes play a critical role in the development of herpes simplex keratitis (HSK). T-cell subsets defined by their expression of various T-cell receptor (TCR) Vß segments were studied following corneal HSV-1 infection (p.i.). • Methods: Conjunctiva, corneal limbus and corneal stroma of two inbred BALB/c congenic mouse strains which differ only in the gene products closely linked to the Igh-1 locus on chromosome 12 were analyzed. • Results: While C.B-17 mice (Igh-1b) were resistant to HSK, C.AL-20 mice (Igh-1d) clinically developed severe necrotizing keratitis by day 11 p.i. The corneal stroma of C.B-17 mice remained clear, while it was increasingly infiltrated by mononuclear cells and neutrophils in C.AL-20 mice by day 11 p.i. In C.B-17 mice, Thy1.2+ cells were found in the conjunctiva between days 2 to 4 p.i., and subsequently decreased. Only a few Thyl.2+ cells were found in the limbus, and no such cells were found in the stroma. In contrast, in C.AL-20 mice the numbers of Thyl.2+ cells (activated CD4+, Vß8+ T cells) profoundly increased in the conjunctiva by day 4 p.i. These cells infiltrated the limbus between days 7 and 11 p.i. and eventually entered the stromal tissue by day 11 p.i. • Conclusions: Our data suggest that the HSV-1-induced corneal tissue destruction is mediated by mononuclear cells and neutrophils and that these cells are probably attracted into the cornea by cytokines elaborated by activated CD4+, Vß8+ T cells.

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References

  1. Aebischer T, Oehen S, Hengartner H (1990) Preferential usage of Va4 and Vß10 T cell receptor genes by lymphocyte choriomeningitis virus glycoprotein-specific H-2Db-restricted cytotoxic T cells. Eur J Immunol 20:523–531

    Google Scholar 

  2. Allison JP, Lanier LL (1987) Structure, function, and serology of the t cell antigen receptor complex. Ann Rev Immunol 5:503–540

    Google Scholar 

  3. Baron S, Worthington MG, Williams J, Gaines JW (1976) Postexposure serum prophylaxis of neonatal herpes simplex virus infection of mice. Nature 261:505–506

    Google Scholar 

  4. Bonneville M, Janeway CA Jr, Kouichi I, Haser W, Ishida I, Nakanishi N, Tonegawa S (1988) Intestinal intraepithelial lymphocytes are a distinct set of gd T cells. Nature 336:479–481

    Google Scholar 

  5. Born WK, Kalataradi H, Modlin RL, O'Brien RL (1991) The role of gd T lymphocytes in infection. Curr Opinion Immunol 3:455–459

    Google Scholar 

  6. Brenner MB, McLean J, Dialynas DP, Strominger JL, Smith JA, Owen FL, Seidman JG, Ip S, Rosen F, Krangel MS (1986) Identification of a putative second T-cell receptor. Nature 322:145–149

    Google Scholar 

  7. Carding SR, Allan W, Kyes S, Hayday A, Bottomly K, Doherty PC (1990) Late dominance of the inflammatory process in murine influenza by gd+ T cells. J Exp Med 172:1225–1231

    Google Scholar 

  8. Centifanto-Fitzgerald YM, Yamaguchi T, Kaufman HE, Tognon M, Roizman B (1982) Ocular disease pattern induced by herpes simplex virus is genetically determined by a specific region of viral DNA. J Exp Med 155:475–489

    Google Scholar 

  9. Centifanto-Fitzgerald YM, Fenger T Kaufman HE (1982) Virus proteins in herpetic keratitis. Exp Eye Res 35:425–441

    Google Scholar 

  10. De Paoli P, Gennari D, Martelli P, Cavarzerani V, Comoretto S, Santini G (1990) gd T cell receptor-bearing lymphocytes during Epstein/Barr virus infection. J Infect Dis 161:1013–1016

    Google Scholar 

  11. Doymaz MZ, Rouse BT (1992) Herpetic stromal keratitis: an immunopathological disease mediated by CD4+ T lymphocytes. Invest Ophthalmol Vis Sci 33:2165–2173

    Google Scholar 

  12. Foster CS, Tsai Y, Monroe JG, Cambell RC, Cestari M, Knipe D, Greene MI (1986) Genetic studies on murine susceptibility to herpes simplex keratitis. Clin Immunol Immunopathol 40:313–320

    Google Scholar 

  13. Greene MI, Nelles MJ, Sy MS, Nisonoff A (1982) Regulation and immunity to the azobenzenearsonate hapten. Adv Immunol 32:253–300

    Google Scholar 

  14. Haskins K, Kubo R, White J, Pigeon M, Kappler JW, Marrack P (1983) The major histocompatibility complex-restricted antigen receptor on T-cells. J Exp Med 157:1149–1169

    Google Scholar 

  15. Hendricks RL, Tumpey TM (1990) Contribution of virus and immune factors to herpes simplex virus type 1 induced corneal pathology. Invest Ophthalmol Vis Sci 30:1929–1939

    Google Scholar 

  16. Hendricks RL, Janowicz M, Tumpey TM (1992) Critical role of corneal Langerhans cells in the CD4- but not CD8-mediated immunopathology in herpes simplex virus-1-infected mouse corneas. J Immunol 148:2522–2529

    Google Scholar 

  17. Janeway CA Jr, Jones B, Hayday A (1988) Specificity and function of T cells bearing gd receptors. Immunol Today 9:73–76

    Google Scholar 

  18. Jayaraman S, Heiligenhaus A, Rodriguez A, Soukiasian S, Dorf ME, Foster CS (1993) Exacerbation of herpes simplex virus-mediated stromal keratitis by cloned interleukin-4 producing T-cells. J Immunol 151: 5777–5789

    Google Scholar 

  19. Ledbetter J, Rouse R, Micklem S, Herzenberg L (1980) T cell subsets defined by expression of Lyt-1, 2, 3 and Thy-1 antigens. J Exp Med 152:280–295

    Google Scholar 

  20. Lopez C (1975) Genetics of natural resistance to herpes virus in mice. Nature 258:152–154

    Google Scholar 

  21. Lopez C (1980) Resistance to HSV-1 in mouse governed by two major, independently segregated, non-H-2 loci. Immunogenetics 11:87–96

    Google Scholar 

  22. Marrack P, Kappler JW (1990) The staphylococcal enterotoxins and their relatives. Science 248:705–711

    Google Scholar 

  23. Metcalf J, Michaelis BA (1984) Herpetic keratitis in inbred mice. Invest Ophthalmol Vis Sci 25:1222–1225

    Google Scholar 

  24. Metcalf JF, Mamilton DS, Reichert RW (1979) Herpetic keratitis in athymic (nude) mice. Infect Immun 26:1164–1172

    CAS  PubMed  Google Scholar 

  25. Newell CK, Martin S, Sendele D, Mercadal CM, Rouse BT (1989) Herpes simplex virus-induced stromal keratitis: role of T-lymphocyte subsets in immunopathology. J Virol 2:769–775

    Google Scholar 

  26. Niemaltowski MG, Rouse BT (1992) Phenotypic and functional studies on ocular T cells during herpetic infections of the eye. J Immunol 148:1864–1870

    Google Scholar 

  27. Niemaltowski MG, Rouse BT (1992) Predominance of Thl cells in ocular tissues during herpetic stromal keratitis. J Immunol 149:3035–3039

    CAS  PubMed  Google Scholar 

  28. Oakes JE, Davis WB, Taylor JA, Weppner WA (1980) Lymphocyte reactivity contributes to protection conferred by specific antibody passively transferred to herpes simplex virus-infected mice. Infect Immun 29:642–649

    Google Scholar 

  29. Opremcak M, Wells PA, Thompson P, Daigle JA, Rice BA, Foster CS (1988) Immunogenetic influence of the Igh-1 phenotype on experimental herpes simplex virus type-1 corneal infection. Invest Ophthalmol Vis Sci 29:749–754

    Google Scholar 

  30. Opremcak EM, Rice BA, Wells PA, Foster CS (1990) Histology and immunohistology of Igh-1-restricted herpes simplex keratitis in BALB/c congenic mice. Invest Ophthalmol Vis Sci 31:305–312

    Google Scholar 

  31. Owen FL, Ju ST, Nisonoff A (1977) Binding of idiotypic determinants of large proportions of thymus derived lymphocytes in idiotypically suppressed mice. Proc Natl Acad Sci USA 74:2084–2088

    Google Scholar 

  32. Raizman MB, Foster CS (1988) Passive transfer of anti-HSV-1 IgG protects against stromal keratitis in mice. Curr Eye Res 7:823–829

    Google Scholar 

  33. Rodewald HR, Koszinowsky UH, Eichmann K, Melchers I (1989) Predominant utilization of Vß8+ T cell receptor genes in the H-2Ld-restricted cytotoxic T cell response against the immediate-early protein pp89 of the murine cytomegalovirus. J Immunol 143:4234–4238

    Google Scholar 

  34. Russell RG, Naisse MP, Larsen HS, Rouse BT (1984) Role of T lymphocytes in the pathogenesis of herpetic stromal keratitis. Invest Ophthalmol Vis Sci 25:938–944

    PubMed  Google Scholar 

  35. Sandstrom IK, Foster CS, Wells PA, Knipe D, Caron L, Greene MI (1986) Previous immunization of mice with herpes simplex virus type-1 strain MP protects against secondary corneal infection. Clin Immunol Immunopathol 40:326–334

    Google Scholar 

  36. Sherman LA, Maleckar JR (1988) Genetic and environmental regulation of the cytolytic T lymphocyte receptor repertoire specific for allaoantigen. Immunol Rev 101:115–131

    Google Scholar 

  37. Stulting RD, Kindle JC, Nahmias AJ (1985) Patterns of herpes simplex keratitis in inbred mice. Invest Ophthalmol Vis Sci 26:1360–1367

    Google Scholar 

  38. Sy MS, Lowy A, Hay Glass K, Janeway CA, Gurish M, Greene MI, Benacerraf B (1984) Chronic treatment with rabbit anti-mouse μ-chain antibody alters the characteristic immunoglobulin heavy-chain restriction. Proc Natl Acad Sci USA 81:3846–3850

    Google Scholar 

  39. Wander AH, Centifanto YM, Kaufman HE (1980) Strain specificity of clinical isolates of herpes simplex virus. Arch Ophthalmol 98:1458–1461

    Google Scholar 

  40. Yanagi Y, Maekawa R, Cook T, Kanagawa O, Oldstone MBA (1990) Restricted V-segment usage in T cell receptors from cytotoxic T lymphocytes specific for a major epitope of lymphocytic choriomeningitis virus. J Virol 64:5919–5926

    Google Scholar 

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Presented as a paper at the ECORA Meeting, 4–7 October 1993, Bonn

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Heiligenhaus, A., Foster, C.S. Histological and immunopathological analysis of T-cells mediating murine HSV-1 keratitis. Graefe's Arch Clin Exp Ophthalmol 232, 628–634 (1994). https://doi.org/10.1007/BF00193124

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  • DOI: https://doi.org/10.1007/BF00193124

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