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Expression of immunity to intravaginal herpes simplex virus type 2 infection in the genital tract and associated lymph nodes

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Summary

Herpes simplex virus type 2 is a human venereal pathogen which causes lethal neurological illness after intravaginal inoculation into BALB/cJ mice. In the present studies, we demonstrate that intravaginal vaccination with an attenuated strain of this virus, which possesses a partial deletion of the thymidine kinase gene, rapidly induced durable immunity to lethal intravaginal challenge with wild-type virus. Such immunity was characterized by a dramatic hyperplasia of genital lymph nodes and a significant reduction in wild-type virus replication and spread from the genital tract following lethal challenge. Of greater importance, immunity to lethal wild-type virus challenge in the genital tract was transferrable to non-immune mice with genital lymph node cells prepared 1 week after intravaginal vaccination but was not transferrable with serum or cells from other lymphoid organs tested at this time. The adoptive transfer of anti-viral immunity to wild-type challenge was also characterized by a diminution in wild-type virus replication and spread from the genital tract. These results suggest that an important component of cellular immunity to genital pathogens may be antigenic stimulation of genital lymph nodes.

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References

  1. Allen WP, Rapp F (1982) Concept review of genital herpes vaccines. J Infect Dis 145: 413–421

    Google Scholar 

  2. Babuik LA, Rouse BT (1979) Immune control of herpes virus latency. Can J Microbiol 25: 267–274

    Google Scholar 

  3. Balachandran N, Bacchetti S, Rawls WE (1982) Protection against lethal challenge of BALB/c mice by passive transfer of monoclonal antibodies to five glycoproteins of herpes simplex virus type 2. Infect Immun 37: 1132–1137

    Google Scholar 

  4. Balachandran N, Harnish D, Rawls WE (1982) Glycoproteins of herpes simplex virus type 2 as defined by monoclonal antibodies. J Virol 44: 344–355

    Google Scholar 

  5. Batty I, Warrack GH (1955) Local antibody production in the mammary gland, spleen, uterus, vagina, and appendix of the rabbit. J Pathol Bacteriol 70: 335–363

    Google Scholar 

  6. Beer AE, Heaves WB (1978) Antigenic status of semen from the viewpoints of the female and the male. Fertil Steril 29: 3–22

    Google Scholar 

  7. Bienenstock J, Befus AD (1980) Mucosal immunology. Immunology 41: 249–270

    Google Scholar 

  8. Bienenstock J, Befus AD, McDermott MR, Mirski S, Rosenthal K, Tagliabue A (1983) The mucosal immunological network: componentalization of lymphocytes, natural killer cells and mast cells. In:McGhee JR, Mestecky J (eds) The secretory immune system. Ann NY Acad Sci, vol 409, pp 164–170

  9. Braciale TJ, Andrew ME, Braciale VL (1981) Heterogeneity and specificity of cloned lines of influenza-virus-specific cytotoxic T lymphocytes. J Exp Med 153: 910–923

    Google Scholar 

  10. Braun RW, Teute HK, Kirchner H, Munk K (1984) Replication of herpes simplex virus in human T lymphocytes: characterization of the viral target cell. J Immunol 132: 914–919

    Google Scholar 

  11. Chipperfield EJ, Evans BA (1972) The influence of local infection on immunoglobulin formation in the human endocervix. Clin Exp Immunol 11: 219–223

    Google Scholar 

  12. Chipperfield EJ, Evans BA (1975) Effect of local infection and oral contraception on immunoglobulins in bovine cervico-vaginal mucus; variation with parenteral immunization and local infection withVibrio fetus. J Reprod Fertil 31: 359–365

    Google Scholar 

  13. Clarke GN (1984) Detection of antispermatozoal antibodies of IgG, IgA and IgM immunoglobulin classes in cervical mucus. Am J Reprod Immunol 6: 195–197

    Google Scholar 

  14. Clark DA, McDermott MR (1981) Active suppression of host-vs-graft reaction in pregnant mice. J Immunol 127: 1267–1273

    Google Scholar 

  15. Clark DA, Slapsys R, Croy BA, Rossant J, McDermott MR (1983) Regulation of cytotoxic T cells in pregnant mice. In:Wegmann T, Gill TJ (eds) Immunology of reproduction. Oxford University Press, New York, pp 343–361

    Google Scholar 

  16. Cook ML, Stevens JG (1983) Restricted replication of herpes simplex virus in spinal ganglia of resistant mice is accompanied by an early infiltration of immunoglobulin G-bearing cells. Infect Immun 40: 752–758

    Google Scholar 

  17. Merrinran H, Woods S, Winter C, Fahnlunder A, Corey L (1984) Secretory IgA in cervicovaginal secretions from women with genital infection due to herpes simplex virus. J Infect Dis 149: 505–510

    Google Scholar 

  18. Eagler H, Zawatzky R, Goldbach A, Schroder CH, Weyland C, Hammerling GJ, Kirchner H (1981) Experimental infections of inbred mice with herpes simplex virus II. Interferon production and activation of natural killer cells in the peritoneal exudate. J Gen Virol 55: 25–30

    Google Scholar 

  19. Emeson EE (1978) Migratory behavior of lymphocytes with specific reactivity to alloantigens II. Selective recruitment to lymphoid cell allografts and their draining lymph nodes. J Exp Med 147: 13–24

    Google Scholar 

  20. Emeson EE, Norrin AJ, Veith FJ (1982) Antigen-induced recruitments of circulating lymphocytes to the lungs and hilar lymph nodes of mice challenged intratracheally with alloantigens. Am Rev Respir Dis 125: 453–459

    Google Scholar 

  21. Favila L, Howes EL, Taylor WA, Mitchison NA (1982) An adoptive cell transfer system for the evaluation of immunity toHerpes Simplex virus in mice. Clin Exp Immunol 48: 307–314

    Google Scholar 

  22. Fitzgerald PSa, Lopez C (1982) Role of interferon in natural kill of herpes virus-infected fibroblasts. In:Herberman RB (ed) NK cells and other natural effector cells. Academic Press, New York, pp 387–393

    Google Scholar 

  23. Harbour DA, Hills TJ, Blyth WA (1981) Acute and recurrent herpes simplex in several strains of mice. J Gen Virol 55: 31–40

    Google Scholar 

  24. Husband AJ, Gowans JL (1978) The origin and antigen-dependent distribution of IgA-containing cells in the intestine. J Exp Med 148: 1146–1160

    Google Scholar 

  25. Kerr WR, Robertson M (1953) Active and passive sensitization of the uterus of the cowin vivo againstTrichomonas foetus antigen and evidence for the local production of antibody in that site. J Hyg 51: 405–415

    Google Scholar 

  26. Larsen HS, Russel RG, Rouse BT (1983) Recovery from lethal herpes simplex virus type 1 infection is mediated by cytotoxic T lymphocytes. Infect Immun 41: 197–204

    Google Scholar 

  27. Leung KN, Nash AA, Sia DY, Wildy P (1984) Clonal analysis of T-cell responses to herpes simplex virus: isolation, characterization and antiviral properties of an antigen-specific helper T-cell clone. Immunology 53: 623–633

    Google Scholar 

  28. Lin YL, Askonas BA (1981) Biological properties of influenza A virus-specific killer T cell clone: inhibition of virus replicationin vivo and induction of delayed-type hypersensitivity reactions. J Exp Med 154: 225–234

    Google Scholar 

  29. Lukacher AE, Braciale VL, Braciale TJ (1984)In vivo effector function of influenza virus-specific cytotoxic T lymphocyte clones is highly specific. J Exp Med 160: 814–876

    Google Scholar 

  30. McDermott MR, Befus AD, Bienenstock J (1982) The structural basis for immunity in the respiratory tract. Int Rev Exp Pathol 23: 48–112

    Google Scholar 

  31. McDermott MR, Bienenstock J (1979) Evidence for a common mucosal immunologic system. I. Migration of B immunoblasts into intestinal, respiratory and genital tissues. J Immunol 122: 1892–1898

    Google Scholar 

  32. McDermott MR, Clark DA, Bienenstock J (1980) Evidence for a common mucosal immunologic system. II. Influence of the estrous cycle on B immunoblast migration into genital and intestinal tissues. J Immunol 124: 2536–2539

    Google Scholar 

  33. McDermott MR, Smiley JR, Brais LP, Rudzrogahe Bienenstock J (1984) Immunity in the female genital tract after intravaginal vaccination of mice with an attenuated strain of herpes simplex virus type 2. J Virol 51: 747–753

    Google Scholar 

  34. Mendis LN, Best JM, Banatvala JG (1981) Class-specific antibodies (IgG and IgA) to membrane antigens of herpes simplex type-2 infected cells in patients with cervical dysplasia and neoplasia. Int J Cancer 27: 669–677

    Google Scholar 

  35. Mogensen SC, Andersen HK (1981) Recovery of mice from herpes simplex virus type 2 hepatitis: adoptive transfer of recovery with immune spleen cells. Infect Immun 33: 743–749

    Google Scholar 

  36. Morahan PS, Morse SS, McGeorge MB (1980) Macrophage extrinsic antiviral activity during herpes simplex virus infection. J gen Virol 46: 291–300

    Google Scholar 

  37. Morahan PS, Thomson TA, Kohl A, Murray BK (1981) Immune responses to labial infection of BALB/c mice with herpes simplex virus type 1. Infect Immun 32: 180–187

    Google Scholar 

  38. Nahmias AJ, Naib ZM, Highsmith AK, Josey WE (1967) Experimental genital herpes simplex infection in the mouse. Pediatr Res 1: 209–210

    Google Scholar 

  39. Nash AA, Ashford NPN (1982) Split T-cell tolerance in herpes simplex virus-infected mice and its implication for anti-viral immunity. Immunology 45: 761–767

    Google Scholar 

  40. Nash AA, Gell PGH (1983) Membrane phenotype of murine effector and suppressor T cells involved in delayed hypersensitivity and protective immunity to herpes simplex virus. Cell Immunology 75: 348–355

    Google Scholar 

  41. Nash AA, Gell PGH, Wildy P (1981) Tolerance and immunity in mice infected with herpes simplex virus: simultaneous induction of protective immunity and tolerance to delayed-type hypersensitivity. Immunology 43: 153–159

    Google Scholar 

  42. Ogra PC, Ogra SS (1973) Local antibody response to polio vaccine in the human female genital tract. J Immunol 110: 1307–1311

    Google Scholar 

  43. Pelton BK, Duncan IB, Denman AM (1980) Herpes simplex virus depresses antibody production by affecting T-cell function. Nature 284: 176–177

    Google Scholar 

  44. Plaeger-Marshall S, Wilson LA, Smith JW (1983) Alteration of rabbit alveolar and peritoneal macrophage function by herpes simplex virus. Infect Immun 41: 1376–1379

    Google Scholar 

  45. Rawls WE (1980) Herpes simplex virus types 1 and 2 and herpes virus simae. In:Lennette EH, Schmidt NJ (eds) Diagnostic procedures for viral, rickettsial, and chlamydial infections. Am Publ Health Assoc Inc, Washington, DC, pp 309–373

    Google Scholar 

  46. Schumacher GFB (1980) Humoral immune factors in the female reproductive tract and their changes during the cycle. In:Dhindsa DS, Schumacher GFB (eds) Immunological aspects of infertility and sterility regulation. Elsevier, North-Holland, New York, pp 93–141

    Google Scholar 

  47. Scott JR, Feldbush TL, Covault JM (1977) A study of maternal lymphoid organs and the progeny following treatment with immunomodulating agents during pregnancy. Clin Exp Immunol 30: 393–402

    Google Scholar 

  48. Seth P, Rawls WE, Duff R, Rapp F, Adam E, Melnick JL (1974) Antigenic differences between isolates of herpes virus type 2. Intervirology 3: 1–14

    Google Scholar 

  49. Sethi KK, Omata Y. Schneweis KE (1983) Protection of mice from fatal herpes simplex type 1 infection by adoptive transfer of cloned virus specific and H-2 restricted cytotoxic T lymphocytes. J gen Virol 64: 443–447

    Google Scholar 

  50. Shore SL, Cromeans TL, Norrild B (1979) Early damage of herpes-infected cells by antibody dependent cellular cytotoxicity: relative roles of virus-specified cell-surface antigens and input virus. J Immunol 123: 2239–2244

    Google Scholar 

  51. Simmons A, Nash AA (1985) Role of antibody in primary and recurrent herpes simplex virus infection. J Virol 53: 944–948

    Google Scholar 

  52. Waldman RH, Cruz JM, Rowe DS (1972) Immunoglobulin levels and antibody toCandida albicans in human cervicovaginal secretions. Clin Exp Immunol 10: 427–434

    Google Scholar 

  53. Walz MA, Price RW, Notkins AL (1974) Latent ganglionic infection with herpes simplex virus types 1 and 2: viral reactivationin vivo after neurectomy. Science 184: 1185–1187

    Google Scholar 

  54. Weisz-Carrington P, Roux ME, McWilliams M, Phillips-Quagliata JM, Lamm ME (1979) Organ and isotype distribution of plasma cells producing specific antibody after oral immunization; evidence for a generalized secretory immune system. J Immunol 123: 1705–1708

    Google Scholar 

  55. Wilkie BN, Duncan JR, Winter AJ (1972) The origin class and specificity of immunoglobulins in bovine cervicovaginal mucus: variation with parenteral immunization and local infection withVibrio fetus. J Reprod Fertil 31: 359–365

    Google Scholar 

  56. Wira CR, Sandoe CP (1977) Sex steroid hormone regulation of IgA and IgG in rat urine secretions. Nature 268: 534–536 (1977)

    Google Scholar 

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Authors and Affiliations

  1. Department of Pathology, McMaster University, Hamilton, Ontario, Canada

    M. R. McDermott, P. Leslie, J. Brais, Gudrun C. Goettsche & M. J. Evelegh

  2. Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada

    C. H. Goldsmith

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  1. M. R. McDermott
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  2. P. Leslie
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  3. J. Brais
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  4. Gudrun C. Goettsche
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  5. M. J. Evelegh
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  6. C. H. Goldsmith
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McDermott, M.R., Leslie, P., Brais, J. et al. Expression of immunity to intravaginal herpes simplex virus type 2 infection in the genital tract and associated lymph nodes. Archives of Virology 93, 51–68 (1987). https://doi.org/10.1007/BF01313893

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  • DOI: https://doi.org/10.1007/BF01313893

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