Lesion T-Cell Response to HSV in HIV Infection

David Koelle, MD

This research study is directed toward defining the mechanisms through which HIV causes severe recurrent HSV infection. Recurrent HSV infection was one of the first opportunistic infections (OI) described for HIV-infected individuals, and HSV infection is responsible for considerable morbidity in HIV-positive patients. However, little is known about the specific mechanisms underlying the susceptibility of HIV-positive individuals to recurrent HSV infection. Recent studies in this laboratory indicate that individuals with early or late HIV infection, as compared to HIV-seronegative individuals, experience more frequent asymptomatic shedding of HSV, and a longer duration of HSV shedding in both symptomatic and asymptomatic reactivation episodes. The frequency and duration of these HSV reactivation episodes does not appear to be solely related to CD4+ lymphocyte counts implicating other elements of the host-specified immune response in the immunopathogenesis of HSV infection. The overall goal of this study is to characterize the host immune responses at cutaneous HSV recurrence sites in HIV-infected persons.

The specific aims of this project are to:

1. Characterize lesion immune responses and peripheral blood mononuclear cell (PBMC) T-lymphocyte responses to HSV in HIV-positive persons
2. Determine if the activation of HSV-specific CD4+ T-cells within recurrent HSV lesions is associated with their destruction by apoptosis or HIV infection
3. Evaluate cytokine patterns within recurrent HSV lesions in HIV-infected persons to determine if T-cells are making the appropriate cytokines
4. Measure the ability of cutaneous antigen-presenting cells (APC) from HIV-infected persons to present antigen to HSV-specific lesion-infiltrating lymphocytes

This laboratory has developed methods to study HSV-specific lesion-infiltrating cells. In HIV-seronegative individuals, this infiltrate includes antigen-specific CD4+ T-cells. Local cytokine responses and T-cell receptor (TCR) gd+ cells reactive with HSV have also been detected in lesions. The investigators will determine if such HSV-specific T-cells are present within lesions in HIV-positive persons.

For each specific aim, responses in HIV-infected persons both with and without severe HSV disease are compared to responses from seronegative persons. The investigators have demonstrated that the frequency of HSV-specific CD8+ pCTL, in PBMC, is significantly lower in HSV-positive, HIV-positive persons than in HSV-positive, HIV-negative persons. In HSV-positive, HIV-positive individuals, patients who had more severe genital herpes recurrences had significantly lower HSV-specific CD8+ pCTL frequencies than those patients with mild recurrences.

Report courtesy of Anna Marie Beckmann

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Recent Publications

Posavad CM, Koelle DM, Shaughnessy MF, Corey L. Severe genital herpes infections in HIV-infected individuals with impaired herpes simplex virus-specific CD8+ cytotoxic T lymphocyte responses. Proc Natl Acad Sci USA 1997; 94:10289-94.