15th International AIDS Conference Bangkok, Thailand - July 11-16, 2004

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. A10325)

Schwartz DH, Iyengar S, Finny JG, Shanmugam A
Johns Hopkins University, Baltimore, United States

BACKGROUND: Innate immunity against HIV has not been extensively studied using PMBCs from normal, unexposed, uninfected individuals. This innate immunity may explain, in part, the low rate of infection per exposure among newly exposed, and may set the stage for persistenty exposed uninfected individuals. It may also help determine the response to infection with HIV, or immunization with vaccines. It is therefore important to quantify the antiviral contribution of various cell subsets in PBMC of normal, unexposed donors.

METHODS: We modified our published in vitgro challenge assay to detect early rounds of infection in a quantitative manner. Replicate PBMC 1 ml cultures were infected with 100 TCID50 BaL (R5) and stimulated 2 hours later with OKT3 + Il-2. On days 1, 2, and 4, supernatant p24 was assayed by EIA. Whole PBMCs were compared with PBMCs depleted of CD8+ T cells, CD14+ monocytes, CD56+ NK cells, or CD10+ B cells. In all cases, the remaining PBMCs contained 45-55% CD4+ lymphocy tes and< 1% residual depleted population.

RESULTS: In 4/4 experiments, CD8 depletion had the expected result of increasing viral production >4-fold by day 2. Surprisingly, CD14+ monocyte depletion increased p24 >10-fold. By contrast, depletion of CD19+ B cells or CD56+ NK cells resulted in up to 75% reduction in virus. In all cases, differences between groups showed a p< 0.01.

CONCLUSIONS: The unanticipated antiviral effect of normal donor monocytes (exceeding the expected antiviral effect of CD8+ T cells) suggests production of high levels of antiviral factors and/or destruction of many internalized virions. Apparent enhanced HIV growth in the presence of NK or B cells is consistent with a role as host cells and/or partial antagonists of monocyte and CD8 mediated aniviral effects. Parallel studies with X4 HIV are in progress and may point to mechanisms.

040711
A10325

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