1887

Abstract

T lymphocytes are the main mediators of the protective immune response in recurrent herpes simplex. Early in the development of recurrent lesions, macrophages and CD4 T lymphocytes predominate in the mononuclear infiltrate surrounding infected epidermal cells. Human epidermal keratinocytes allow herpes simplex virus type 1 (HSV-1) replication and human leukocyte antigen (HLA)-DR is strongly expressed , their pretreatment with IFN- induced HLA-DR expression and partially reversed major histocompatibility complex class I down-regulation by the virus. Mononuclear cell cytotoxicity for these cells was mediated predominantly by CD4 and also by CD8 T cells. Late HSV-1 proteins were the major targets for CD4 CTL, while CD8 CTL predominantly targeted early HSV-1 proteins. Here it is shown that both mononuclear and CD4 CTL consistently recognized the major HSV-1 glycoproteins, gB, gC, gD and gH, using IFN--pretreated keratinocytes infected with vaccinia virus-HSV glycoprotein recombinants (VvgB, VvgC, VvgD or VvgH). CD4 cytotoxicity was highest for VvgD-infected keratinocytes, followed by VvgB or VvgC and then VvgH in seven patients. CD4 CTL from two of 13 patients also recognized an epitope in the HSV tegument protein VP16, demonstrated by comparing cytotoxicity for the partial deletion mutants RP3 or RP4 and the parental RP1 HSV strain. In summary, the major HSV glycoproteins gB, gC and gD were consistently the major targets for CD4 CTL in VvgB-, VvgC-, VvgD- and VvgH-infected, IFN--pretreated human epidermal keratinocytes .

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1998-02-01
2024-04-16
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References

  1. Basham T. Y., Nickoloff B. J., Merigan T. C., Morhenn V. B. 1984; Recombinant γ interferon induces HLA-DR expression on cultured human keratinocytes. Journal of Investigative Dermatology 83:88–90
    [Google Scholar]
  2. Basham T. Y., Nickoloff B. J., Merigan T. C., Morhenn V. B. 1985; Recombinant gamma interferon differentially regulates class II antigen expression and biosynthesis on cultured human keratinocytes. Journal of Interferon Research 5:23–32
    [Google Scholar]
  3. Bastin C., Hermand P., Francotte M., Garcon N., Slaoui M., Pala P. 1994; Synergistic association of adjuvants QS21 and MPL for induction of cytolytic T lymphocytes and T helper responses to recombinant protein antigens. In Abstractsofthe 34thInterscience Conference on Antimicrobial Agents and Chemotherapy of the American Society for Microbiology Abstr. G41 Washington, DC: American Society for Microbiology;
    [Google Scholar]
  4. Cantin E. M., Eberle R., Boldick J. L., Moss B., Willey D. E., Notkins A. R., Openshaw H. 1987; Expression of HSV glycoprotein B by a recombinant vaccinia virus and protection of mice against lethal HSV-1 infection. Proceedings of National Academy of Sciences, USA 84:5908–5912
    [Google Scholar]
  5. Cress W. D., Triezenberg S. J. 1990; Critical structural elements of the VP16 transcriptional activation domain. Science 251:87–90
    [Google Scholar]
  6. Cunningham A. L., Merigan T. C. 1983; Gamma interferon production appears to predict time of recurrence of herpes labialis. Journal of Immunology 130:2397–2400
    [Google Scholar]
  7. Cunningham A. L., Merigan T. C. 1984; Leu3 T-cells produce gamma-interferon in patients with recurrent herpes labialis. Journal of Immunology 132:197–202
    [Google Scholar]
  8. Cunningham A. L., Noble J. R. 1989; Role of keratinocytes in human recurrent herpetic lesions. Journal of Clinical Investigation 83:490–496
    [Google Scholar]
  9. Cunningham A. L., Turner R. R., Miller A. C., Para M. F., Merigan T. C. 1985; Evolution of recurrent herpes simplex lesions: an immunohistologic study. Journal of Clinical Investigation 75:226–233
    [Google Scholar]
  10. Fauci A. S. 1988; The human immunodeficiency virus: infectivity and mechanisms of pathogenesis. Science 239:617–622
    [Google Scholar]
  11. Fitzgerald-Bocarsly P., Howell D. M., Pettera L., Tehrani S., Lopez C. 1991; Immediate-early gene expression is sufficient for induction of natural killer cell-mediated lysis of herpes simplex virus type 1 infected fibroblasts. Journal of Virology 65:3151–3160
    [Google Scholar]
  12. Forrester A. J., Sullivan V., Simmons A., Blacklaws B. A., Smith G. L., Nash A. A., Minson A. C. 1991; Induction of protective immunity with antibody to herpes simplex virus type 1 glycoprotein H (gH) and analysis of the immune response to gH expressed in recombinant vaccinia virus. Journal of General Virology 72:369–375
    [Google Scholar]
  13. Fruh K., Ahn K., Djaballah H., Sempe P., van Endert P. M., Tampe R., Peterson P. A., Yang Y. 1995; A viral inhibitor of peptide transporters for antigen presentation. Nature 375:415–418
    [Google Scholar]
  14. Hill A., Jugovic P., York I., Russ G., Bennink J., Yewdell J., Ploegh H., Johnson D. C. 1995; Herpes simplex virus turns off TAP to evade host immunity. Nature 375:411–415
    [Google Scholar]
  15. Koelle D. M., Tigges M. A., Burke R. L., Symington F. W., Ridell S. R., Abbo H., Corey L. 1993; Herpes simplex virus infection of human fibroblasts and keratinocytes inhibits recognition by cloned CD8 cytotoxic T-lymphocytes. Journal of Clinical Investigation 91:961–968
    [Google Scholar]
  16. Koelle D. M., Abbo H., Peck A., Ziegweid K., Corey L. 1994a; Direct recovery of herpes simplex virus (HSV)-specific T-lymphocyte clones from recurrent genital HSV-2 lesions. Journal of Infectious Diseases 169:956–961
    [Google Scholar]
  17. Koelle D. M., Corey L., Burke R. L., Eisenberg R. J., Cohen G. H., Pichyangkura R., Triezenberg S. J. 1994b; Antigenic specificities of human CD4 T cell clones recovered from recurrent genital herpes simplex virus type 2 lesions. Journal of Virology 68:2803–2810
    [Google Scholar]
  18. Lawman J. R., Rouse B. T., Courtney R. J., Walker R. D. 1980; Cell-mediated immunity against herpes simplex virus : induction of cytotoxic T lymphocytes. Infection and Immunity 27:133–139
    [Google Scholar]
  19. Martin S., Courtney R. J., Fowler G., Rouse B. T. 1988; Herpes simplex virus type 1 specific cytotoxic T lymphocytes recognize viral nonstructural proteins. Journal of Virology 62:2265–2273
    [Google Scholar]
  20. Martin S., Mercadal C. M., Weir J. P., Rouse B. T. 1993; The proportion of herpes simplex virus specific cytotoxic T lymphocytes (Tc) that recognise glycoprotein C varies between individual mice and is dependent on the form of immunisation. Viral Immunology 6:21–33
    [Google Scholar]
  21. Mikloska Z., Kesson A. M., Penfold M. E. T., Cunningham A. L. 1996; Herpes simplex virus protein targets for CD4 and CD8 lymphocyte cytotoxicity in cultured epidermal keratinocytes treated with interferon-γ. Journal of Infectious Diseases 173:7–17
    [Google Scholar]
  22. Nash A. A., Jayasuriya A., Phelan J., Cobbold S. P., Waldmann H., Prospero T. 1987; Different roles for L3T4+ and Lyt 2+ T cell subsets in the control of an acute herpes simplex virus infection of the skin and nervous system. Journal of General Virology 68:825–833
    [Google Scholar]
  23. Overall J. C., Spruance S. L., Green J. A. 1981; Viral-induced leukocyte interferon in vesicle fluid from lesions of recurrent herpes labialis. Journal of Infectious Diseases 143:543–547
    [Google Scholar]
  24. Oxenius A., Bachmann M. F., Ashton-Rickardt P. G., Tonegawa S., Zinkernagel R. M., Hengartner H. 1995; Presentation of endogenous viral proteins in association with major histocompatibility complex II : on the role of intracellular compartmentalization, invariant chain and the TAP transporter system. European Journal of Immunology 25:3402–3411
    [Google Scholar]
  25. Posavad C. M., Rosenthal K. L. 1992; Herpes simplex virus- infected human fibroblasts are resistant to and inhibit cytotoxic T- lymphocyte activity. Journal of Virology 66:6264–6272
    [Google Scholar]
  26. Posavad C. M., Newton J. J., Rosenthal K. L. 1993; Inhibition of human CTL-mediated lysis by fibroblasts infected with herpes simplex virus. Journal of Immunology 151:4865–4873
    [Google Scholar]
  27. Posavad C. M., Koelle D. M., Corey L. 1996; High frequency of CD8 cytotoxic T lymphocyte precursors specific for herpes simplex viruses in persons with genital herpes. Journal of Virology 70:8165–8168
    [Google Scholar]
  28. Reeves W. C., Corey L., Adams H. G., Vontver L. A., Holmes K. K. 1981; Risk of recurrence after first episodes of genital herpes. New England Journal of Medicine 305:315–319
    [Google Scholar]
  29. Schmid D. S., Rouse B. T. 1992; The role of T cell immunity in control of herpes simplex virus. In Herpes Simplex Virus . Pathogenesis, Immunobiology and Control pp 57–74 Rouse B. T. Edited by Berlin: Springer-Verlag;
    [Google Scholar]
  30. Siegal F. P., Lopez C., Hammer G. S., Brown A. E., Kornfeld S. J., Gold J., Hassett J., Hirschman S. Z., Cunningham-Rundles C., Adelsberg B. R. 1981; Severe acquired immunodefiecency in male homosexuals, manifested by chronic perianal ulcerative herpes simplex lesions. New England Journal of Medicine 305:1439–1444
    [Google Scholar]
  31. Spruance S. L., Overall J. C., Kern E. R., Krueger G. G., Pliam V., Miller W. 1977; The natural history of recurrent herpes simplex labialis. New England Journal of Medicine 297:69–75
    [Google Scholar]
  32. Stanberry L. R. 1992; Pathog enesis of herpes simplex virus infection and animal models for its study. In Herpes Simplex Virus . Pathogenesis, Immunobiology and Control pp 15–30 Rouse B. T. Edited by Berlin: Springer-Verlag;
    [Google Scholar]
  33. Straus S. E., Corey L., Burke R. L., Savarese B., Barnum G., Krause P. R., Kost R. G., Meier J. L., Sekulovich R., Adair S.F. others 1994; Placebo-controlled trial of vaccination with recombinant glycoprotein D of herpes simplex virus type 2 for immunotherapy of genital herpes. Lancet 343:1460–1463
    [Google Scholar]
  34. Torseth J. W., Merigan T. C. 1986; Significance of local gamma interferon in recurrent herpes simplex infection. Journal of Infectious Diseases 153:979–984
    [Google Scholar]
  35. Ward P. L., Roizman B. 1994; Herpes simplex genes: the blueprint of a successful human pathogen. Trends in Genetics 10:267–274
    [Google Scholar]
  36. Weinheimer S. P., Boyd B. A., Durham S. K., Resnick J. L., O’Boyle D. R. 1992; Deletion of VP16 open reading frame of herpes simplex virus type 1. Journal of Virology 66:258–269
    [Google Scholar]
  37. York I. A., Roop C., Andrews D. W., Riddell S. R., Graham F. L., Johnson D. C. 1994; A cytosolic herpes simplex virus protein inhibits antigen presentation to CD8 T-lymphocytes. Cell 77:525–535
    [Google Scholar]
  38. Zarling J. M., Moran P. A., Burke R. L., Pachl C., Berman P. W., Lasky L. A. 1986; Human cytotoxic T-cells directed against herpes simplex virus-infected cells. IV. Recognition and activation by cloned glycoproteins gB and gD. Journal of Immunology 136:4669–4673
    [Google Scholar]
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