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Severe genital herpes infections in HIV-infected individuals with impaired herpes simplex virus-specific CD8+ cytotoxic T lymphocyte responses.
Title | Severe genital herpes infections in HIV-infected individuals with impaired herpes simplex virus-specific CD8+ cytotoxic T lymphocyte responses. |
Publication Type | Journal Article |
Year of Publication | 1997 |
Authors | Posavad, CM, Koelle, DM, Shaughnessy, MF, Corey, L |
Journal | Proc Natl Acad Sci U S A |
Volume | 94 |
Issue | 19 |
Pagination | 10289-94 |
Date Published | 1997 Sep 16 |
ISSN | 0027-8424 |
Keywords | CD8-Positive T-Lymphocytes, Cell Line, Transformed, Cross-Sectional Studies, Cytotoxicity, Immunologic, Female, Herpes Genitalis, Herpesvirus 2, Human, HIV Infections, Humans, Male |
Abstract | The specific mechanisms underlying the varied susceptibility of HIV-infected (HIV+) individuals to opportunistic infections (OI) are still incompletely understood. One hypothesis is that quantitative differences in specific T cell responses to a colonizing organism determine the development of an AIDS-defining OI. We evaluated this hypothesis for herpes simplex virus (HSV) infection, a common OI in HIV+ patients. Using limiting dilution analyses, the frequency of HSV-specific CD8+ cytotoxic T lymphocyte precursors (pCTL) and proliferative precursors were quantitated in peripheral blood mononuclear cells from 20 patients coinfected with HIV and HSV-2. The frequency of HSV-specific CD8+ pCTL in HSV+HIV+ individuals was significantly lower than in HSV+HIV- individuals (1 in 77,000 vs. 1 in 6,000, P = .0005) and was not different than in HSV-HIV- individuals (1 in 100,000, P = .24). HIV+ patients who suffered more severe genital herpes recurrences had significantly lower HSV-specific CD8+ pCTL frequencies than those patients with mild recurrences (1 in 170,000 vs. 1 in 26,000, P = .03). In contrast, no significant difference was seen in proliferative precursor frequencies between those patients with mild vs. severe genital herpes (1 in 3,800 vs. 1 in 6,600, P > .5). Quantitative differences in pCTL frequency to HSV appear to be the most important host factor influencing the frequency and severity of HSV reactivation in HIV+ patients. Studies to reconstitute such immunity, especially in people with acyclovir-resistant HSV, appear warranted. |
Alternate Journal | Proc. Natl. Acad. Sci. U.S.A. |
PubMed ID | 9294203 |