Abstract
Herpes simplex virus infection of the scarified dermis results in infection of the nervous system and, subsequently, a cutaneous lesion in the innervated dermatome. We compared the pathogenesis of such zosteriform lesions in mice lacking or severely depleted of CD4+ or CD8+ T cells because of targeted gene disruption. Mice without CD4+ cells showed markedly increased susceptibility, whereas beta 2 microglobulin knockout mice lacking CD8+ T cells were as resistant to challenge as were immunocompetent mice with the same genetic background. Our results demonstrate that CD4+ T cells are of primary importance in the control of herpes simplex virus infections of the skin and nervous system.
Full Text
The Full Text of this article is available as a PDF (148.8 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Banks T. A., Rouse B. T. Herpesviruses--immune escape artists? Clin Infect Dis. 1992 Apr;14(4):933–941. doi: 10.1093/clinids/14.4.933. [DOI] [PubMed] [Google Scholar]
- Grusby M. J., Auchincloss H., Jr, Lee R., Johnson R. S., Spencer J. P., Zijlstra M., Jaenisch R., Papaioannou V. E., Glimcher L. H. Mice lacking major histocompatibility complex class I and class II molecules. Proc Natl Acad Sci U S A. 1993 May 1;90(9):3913–3917. doi: 10.1073/pnas.90.9.3913. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kapoor A. K., Nash A. A., Wildy P., Phelan J., McLean C. S., Field H. J. Pathogenesis of herpes simplex virus in congenitally athymic mice: the relative roles of cell-mediated and humoral immunity. J Gen Virol. 1982 Jun;60(Pt 2):225–233. doi: 10.1099/0022-1317-60-2-225. [DOI] [PubMed] [Google Scholar]
- Lamousé-Smith E., Clements V. K., Ostrand-Rosenberg S. Beta 2M-/- knockout mice contain low levels of CD8+ cytotoxic T lymphocyte that mediate specific tumor rejection. J Immunol. 1993 Dec 1;151(11):6283–6290. [PubMed] [Google Scholar]
- Manickan E., Francotte M., Kuklin N., Dewerchin M., Molitor C., Gheysen D., Slaoui M., Rouse B. T. Vaccination with recombinant vaccinia viruses expressing ICP27 induces protective immunity against herpes simplex virus through CD4+ Th1+ T cells. J Virol. 1995 Aug;69(8):4711–4716. doi: 10.1128/jvi.69.8.4711-4716.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mercadal C. M., Slaoui M., Brown S. M., Rouse B. T. Efficacy of the herpes simplex virus types 1 and 2 mutant viruses to confer protection against zosteriform spread in mice. Viral Immunol. 1993 Spring;6(1):35–42. doi: 10.1089/vim.1993.6.35. [DOI] [PubMed] [Google Scholar]
- Mester J. C., Glorioso J. C., Rouse B. T. Protection against zosteriform spread of herpes simplex virus by monoclonal antibodies. J Infect Dis. 1991 Feb;163(2):263–269. doi: 10.1093/infdis/163.2.263. [DOI] [PubMed] [Google Scholar]
- Niemialtowski M. G., Godfrey V. L., Rouse B. T. Quantitative studies on CD4+ and CD8+ cytotoxic T lymphocyte responses against herpes simplex virus type 1 in normal and beta 2-m deficient mice. Immunobiology. 1994 Apr;190(3):183–194. doi: 10.1016/s0171-2985(11)80268-8. [DOI] [PubMed] [Google Scholar]
- Schmid D. S., Rouse B. T. The role of T cell immunity in control of herpes simplex virus. Curr Top Microbiol Immunol. 1992;179:57–74. doi: 10.1007/978-3-642-77247-4_4. [DOI] [PubMed] [Google Scholar]
- Simmons A., Nash A. A. Zosteriform spread of herpes simplex virus as a model of recrudescence and its use to investigate the role of immune cells in prevention of recurrent disease. J Virol. 1984 Dec;52(3):816–821. doi: 10.1128/jvi.52.3.816-821.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Simmons A., Tscharke D. C. Anti-CD8 impairs clearance of herpes simplex virus from the nervous system: implications for the fate of virally infected neurons. J Exp Med. 1992 May 1;175(5):1337–1344. doi: 10.1084/jem.175.5.1337. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Smith P. M., Wolcott R. M., Chervenak R., Jennings S. R. Control of acute cutaneous herpes simplex virus infection: T cell-mediated viral clearance is dependent upon interferon-gamma (IFN-gamma). Virology. 1994 Jul;202(1):76–88. doi: 10.1006/viro.1994.1324. [DOI] [PubMed] [Google Scholar]
- York I. A., Roop C., Andrews D. W., Riddell S. R., Graham F. L., Johnson D. C. A cytosolic herpes simplex virus protein inhibits antigen presentation to CD8+ T lymphocytes. Cell. 1994 May 20;77(4):525–535. doi: 10.1016/0092-8674(94)90215-1. [DOI] [PubMed] [Google Scholar]