PMID- 8145530 OWN - NLM STAT- MEDLINE DCOM- 19940505 LR - 20220408 IS - 0023-6837 (Print) IS - 0023-6837 (Linking) VI - 70 IP - 3 DP - 1994 Mar TI - A mouse model for studies of mucosal immunity to vaginal infection by herpes simplex virus type 2. PG - 369-80 AB - BACKGROUND: The role of mucosal immunity in defense of the female genital tract against pathogens such as herpes simplex virus-2 (HSV-2) is poorly understood. Here we explored the use of a new mouse model to determine whether local immune events in the vagina of immune animals may protect them against genital herpes. EXPERIMENTAL DESIGN: The effect of the estrous cycle, pregnancy, and sex hormones on vaginal infection of adult mice by HSV-2 was determined by immunolabeling of virus proteins. The immune response to infection was studied by immunolabeling of T lymphocytes, B lymphocytes, and plasma cells in the vagina of infected mice. RESULTS: Inoculation of attenuated virus (TK-HSV-2) or wild-type virus (TK+HSV-2) into the vagina on day 6 of pregnancy or after treatment with Depo-Provera (DP) caused infection of the vaginal epithelium. In contrast, these viruses did not cause infection after vaginal inoculation at estrus, metestrus, or after treatment with Depo-Estradiol. Infected mice showed immunolabeling of virus in the vaginal epithelium from 24 hrs to 5 days after virus inoculation. The immune response to infection included upregulation of class II MHC antigen in vaginal epithelium, CD8+ T cells in epithelium and stroma, and plasma cells and lymphoid nodules in the stroma. Mice that were infected with TK-HSV-2 did not exhibit infection of vaginal epithelium when challenged 6 weeks later with TK+HSV-2. CONCLUSIONS: Progesterone-dominated adult mice become infected after intravaginal inoculation with HSV-2, but estradiol-dominated mice are refractory. Vaginal infection with attenuated HSV-2 produces immunity that protects mice against later infection by wild-type virus. This immunity either prevents infection of vaginal epithelium or severely inhibits viral replication in the epithelium. The observations suggest that the E/DP-treated adult mouse should be a useful model for studies of mucosal immunity to vaginal infection by HSV-2. FAU - Parr, M B AU - Parr MB AD - Southern Illinois University, Carbondale. FAU - Kepple, L AU - Kepple L FAU - McDermott, M R AU - McDermott MR FAU - Drew, M D AU - Drew MD FAU - Bozzola, J J AU - Bozzola JJ FAU - Parr, E L AU - Parr EL LA - eng GR - HD-17737/HD/NICHD NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Lab Invest JT - Laboratory investigation; a journal of technical methods and pathology JID - 0376617 RN - 4TI98Z838E (Estradiol) RN - C2QI4IOI2G (Medroxyprogesterone Acetate) SB - IM MH - Animals MH - B-Lymphocytes/immunology MH - *Disease Models, Animal MH - Estradiol/pharmacology MH - Estrus/immunology MH - Female MH - Herpes Genitalis/*immunology MH - Herpesvirus 2, Human/*immunology MH - Immunity/drug effects MH - Medroxyprogesterone Acetate/pharmacology MH - Mice MH - *Mice, Inbred BALB C MH - Mucous Membrane/immunology MH - Plasma Cells/immunology MH - Pregnancy MH - Pregnancy Complications, Infectious/immunology MH - T-Lymphocytes/immunology MH - Vagina/*immunology EDAT- 1994/03/01 00:00 MHDA- 1994/03/01 00:01 CRDT- 1994/03/01 00:00 PHST- 1994/03/01 00:00 [pubmed] PHST- 1994/03/01 00:01 [medline] PHST- 1994/03/01 00:00 [entrez] PST - ppublish SO - Lab Invest. 1994 Mar;70(3):369-80.