Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1985 Jan;75(1):226–233. doi: 10.1172/JCI111678

Evolution of recurrent herpes simplex lesions. An immunohistologic study.

A L Cunningham, R R Turner, A C Miller, M F Para, T C Merigan
PMCID: PMC423430  PMID: 3880773

Abstract

We performed immunoperoxidase stains on skin biopsies taken from nine patients with recurrent peripheral herpes simplex lesions at 12 h to 6 d after onset of signs of symptoms to phenotype the inflammatory infiltrate, to detect cells producing interferons alpha and gamma, and to locate herpes simplex virus antigen-containing cells. Viral glycoprotein antigen was located in the nuclei and cytoplasm of necrotic epidermal cells, often within vesicles, in biopsies taken between the first and third day. Histologically, biopsies of all stages showed intradermal focal perivascular and diffuse mononuclear inflammatory infiltrates. The cells constituting the infiltrates were predominantly T lymphocytes with lesser numbers of histiocytes; Leu 7+ (most natural killer/killer) cells and B cells were rare in the biopsy specimens. Leu 3a+ ("helper") T lymphocytes predominated in both subepidermal and perivascular regions of early lesions (12-24 h). Tissue helper/suppressor ratios ranged from 6.3 to 3.4 compared with 1.9-1.0 in blood. In later lesions (after 2 d), monocytes/macrophages were more prominent in tissue sections and the helper/suppressor ratios (2.3-2.5) more nearly approximated those of blood (1.6-2.7). The negative correlation of tissue ratios with time was significant (P less than or equal to 0.02). A large proportion of the infiltrated T lymphocytes expressed DR antigens. There was also diffuse strong DR expression on epidermal cells in five cases (all of two or more days). In six biopsies, scattered macrophages and small cells, presumably lymphocytes, demonstrated cytoplasmic or membrane staining for a substance which copurifies with interferon gamma. We identified such stained cells within vessels, suggesting that these cells circulate. Gamma interferon might have an important role within the herpetic lesions, possibly inducing macrophage activation and cytotoxic T lymphocytes and increasing DR expression on monocyte and epidermal cells.

Full text

PDF
226

Images in this article

230Image
on p.230
230Image
on p.230
230Image
on p.230
230Image
on p.230

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abo T., Balch C. M. A differentiation antigen of human NK and K cells identified by a monoclonal antibody (HNK-1). J Immunol. 1981 Sep;127(3):1024–1029. [PubMed] [Google Scholar]
  2. Braathen L. R., Berle E., Mobech-Hanssen U., Thorsby E. Studies on human epidermal Langerhans' cells: II. Activation of human T lymphocytes to herpes simplex virus. Acta Derm Venereol. 1980;60(5):381–387. [PubMed] [Google Scholar]
  3. Carter V. C., Schaffer P. A., Tevethia S. S. The involvement of herpes simplex virus type 1 glycoproteins in cell-mediated immunity. J Immunol. 1981 May;126(5):1655–1660. [PubMed] [Google Scholar]
  4. Cunningham A. L., Merigan T. C. Leu-3+ T cells produce gamma-interferon in patients with recurrent herpes labialis. J Immunol. 1984 Jan;132(1):197–202. [PubMed] [Google Scholar]
  5. Cunningham A. L., Merigan T. C. gamma Interferon production appears to predict time of recurrence of herpes labialis. J Immunol. 1983 May;130(5):2397–2400. [PubMed] [Google Scholar]
  6. Dimitriu-Bona A., Burmester G. R., Waters S. J., Winchester R. J. Human mononuclear phagocyte differentiation antigens. I. Patterns of antigenic expression on the surface of human monocytes and macrophages defined by monoclonal antibodies. J Immunol. 1983 Jan;130(1):145–152. [PubMed] [Google Scholar]
  7. Evans R. L., Wall D. W., Platsoucas C. D., Siegal F. P., Fikrig S. M., Testa C. M., Good R. A. Thymus-dependent membrane antigens in man: inhibition of cell-mediated lympholysis by monoclonal antibodies to TH2 antigen. Proc Natl Acad Sci U S A. 1981 Jan;78(1):544–548. doi: 10.1073/pnas.78.1.544. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Farrar W. L., Johnson H. M., Farrar J. J. Regulation of the production of immune interferon and cytotoxic T lymphocytes by interleukin 2. J Immunol. 1981 Mar;126(3):1120–1125. [PubMed] [Google Scholar]
  9. Fleischmann W. R., Jr, Georgiades J. A., Osborne L. C., Johnson H. M. Potentiation of interferon activity by mixed preparations of fibroblast and immune interferon. Infect Immun. 1979 Oct;26(1):248–253. doi: 10.1128/iai.26.1.248-253.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gatenby P. A., Kansas G. S., Xian C. Y., Evans R. L., Engleman E. G. Dissection of immunoregulatory subpopulations of T lymphocytes within the helper and suppressor sublineages in man. J Immunol. 1982 Nov;129(5):1997–2000. [PubMed] [Google Scholar]
  11. Huff J. C., Krueger G. G., Overall J. C., Jr, Copeland J., Spruance S. L. The histopathologic evolution of recurrent herpes simplex labialis. J Am Acad Dermatol. 1981 Nov;5(5):550–557. doi: 10.1016/s0190-9622(81)70115-4. [DOI] [PubMed] [Google Scholar]
  12. Issekutz T., Chu E., Geha R. S. Antigen presentation by human B cells: T cell proliferation induced by Epstein Barr virus B lymphoblastoid cells. J Immunol. 1982 Oct;129(4):1446–1450. [PubMed] [Google Scholar]
  13. Johnson H. M., Farrar W. L. The role of a gamma interferon-like lymphokine in the activation of T cells for expression of interleukin 2 receptors. Cell Immunol. 1983 Jan;75(1):154–159. doi: 10.1016/0008-8749(83)90314-3. [DOI] [PubMed] [Google Scholar]
  14. Lampert I. A., Suitters A. J., Chisholm P. M. Expression of Ia antigen on epidermal keratinocytes in graft-versus-host disease. Nature. 1981 Sep 10;293(5828):149–150. doi: 10.1038/293149a0. [DOI] [PubMed] [Google Scholar]
  15. Lampson L. A., Levy R. Two populations of Ia-like molecules on a human B cell line. J Immunol. 1980 Jul;125(1):293–299. [PubMed] [Google Scholar]
  16. Murphy G. F., Bhan A. K., Sato S., Harrist T. J., Mihm M. C., Jr Characterization of Langerhans cells by the use of monoclonal antibodies. Lab Invest. 1981 Nov;45(5):465–468. [PubMed] [Google Scholar]
  17. Noble A. G., Lee G. T., Sprague R., Parish M. L., Spear P. G. Anti-gD monoclonal antibodies inhibit cell fusion induced by herpes simplex virus type 1. Virology. 1983 Aug;129(1):218–224. doi: 10.1016/0042-6822(83)90409-9. [DOI] [PubMed] [Google Scholar]
  18. Openshaw H., Asher L. V., Wohlenberg C., Sekizawa T., Notkins A. L. Acute and latent infection of sensory ganglia with herpes simplex virus: immune control and virus reactivation. J Gen Virol. 1979 Jul;44(1):205–215. doi: 10.1099/0022-1317-44-1-205. [DOI] [PubMed] [Google Scholar]
  19. Overall J. C., Jr, Spruance S. L., Green J. A. Viral-induced leukocyte interferon in vesicle fluid from lesions of recurrent herpes labialis. J Infect Dis. 1981 Apr;143(4):543–547. doi: 10.1093/infdis/143.4.543. [DOI] [PubMed] [Google Scholar]
  20. Para M. F., Zezulak K. M., Conley A. J., Weinberger M., Snitzer K., Spear P. G. Use of monoclonal antibodies against two 75,000-molecular-weight glycoproteins specified by herpes simplex virus type 2 in glycoprotein identification and gene mapping. J Virol. 1983 Mar;45(3):1223–1227. doi: 10.1128/jvi.45.3.1223-1227.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pereira L., Dondero D. V., Gallo D., Devlin V., Woodie J. D. Serological analysis of herpes simplex virus types 1 and 2 with monoclonal antibodies. Infect Immun. 1982 Jan;35(1):363–367. doi: 10.1128/iai.35.1.363-367.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Roberts W. K., Vasil A. Evidence for the identity of murine gamma interferon and macrophage activating factor. J Interferon Res. 1982;2(4):519–532. doi: 10.1089/jir.1982.2.519. [DOI] [PubMed] [Google Scholar]
  23. Rosenberg G. L., Notkins A. L. Induction of cellular immunity to herpes simplex virus: relationship to the humoral immune response. J Immunol. 1974 Mar;112(3):1019–1025. [PubMed] [Google Scholar]
  24. Ross G. D. Identification of human lymphocyte subpopulations by surface marker analysis. Blood. 1979 May;53(5):799–811. [PubMed] [Google Scholar]
  25. Sheridan J. F., Donnenberg A. D., Aurelian L., Elpern D. J. Immunity to herpes simplex virus type 2. IV. Impaired lymphokine production during recrudescence correlates with an imbalance in T lymphocyte subsets. J Immunol. 1982 Jul;129(1):326–331. [PubMed] [Google Scholar]
  26. Spruance S. L., Overall J. C., Jr, Kern E. R., Krueger G. G., Pliam V., Miller W. The natural history of recurrent herpes simplex labialis: implications for antiviral therapy. N Engl J Med. 1977 Jul 14;297(2):69–75. doi: 10.1056/NEJM197707142970201. [DOI] [PubMed] [Google Scholar]
  27. Staehelin T., Durrer B., Schmidt J., Takacs B., Stocker J., Miggiano V., Stähli C., Rubinstein M., Levy W. P., Hershberg R. Production of hybridomas secreting monoclonal antibodies to the human leukocyte interferons. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1848–1852. doi: 10.1073/pnas.78.3.1848. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Stein H., Gerdes J., Mason D. Y. The normal and malignant germinal centre. Clin Haematol. 1982 Oct;11(3):531–559. [PubMed] [Google Scholar]
  29. Steinmann G., Conlon P., Hefeneider S., Gillis S. Serological visualization of interleukin 2. Science. 1983 Jun 10;220(4602):1188–1190. doi: 10.1126/science.6344215. [DOI] [PubMed] [Google Scholar]
  30. Tjernlund U. M. Epidermal expression of HLA-DR antigens in mycosis fungoides. Arch Dermatol Res. 1978 Feb 15;261(1):81–86. doi: 10.1007/BF00455380. [DOI] [PubMed] [Google Scholar]
  31. Tjernlund U. M. Ia-like antigens in lichen planus. Acta Derm Venereol. 1980;60(4):309–314. doi: 10.2340/0001555560309314. [DOI] [PubMed] [Google Scholar]
  32. Traugott U., Reinherz E. L., Raine C. S. Multiple sclerosis: distribution of T cell subsets within active chronic lesions. Science. 1983 Jan 21;219(4582):308–310. doi: 10.1126/science.6217550. [DOI] [PubMed] [Google Scholar]
  33. Wood G. S., Warner N. L., Warnke R. A. Anti-Leu-3/T4 antibodies react with cells of monocyte/macrophage and Langerhans lineage. J Immunol. 1983 Jul;131(1):212–216. [PubMed] [Google Scholar]
  34. Yam L. T., Li C. Y., Crosby W. H. Cytochemical identification of monocytes and granulocytes. Am J Clin Pathol. 1971 Mar;55(3):283–290. doi: 10.1093/ajcp/55.3.283. [DOI] [PubMed] [Google Scholar]
  35. Yip Y. K., Barrowclough B. S., Urban C., Vilcek J. Molecular weight of human gamma interferon is similar to that of other human interferons. Science. 1982 Jan 22;215(4531):411–413. doi: 10.1126/science.6173921. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES