The central hypothesis of this proposal is that infection of dendritic cells (DC) occurs early in HIV-infected individuals and that such infection impairs the ability of DC to present antigens to T cells. New methods for obtaining and maintaining highly purified populations of DC will be used. DC will be identified on the basis of phenotype and morphology. The ability of lymphocyte-tropic and monocyte-tropic strains of HIV-1 to infect DC will be compared. Infection will be monitored with assays for p24 antigen production, reverse transcriptase activity, immunofluorescence, electron microscopy, and in-situ hybridization for HIV RNA and DNA. The function of uninfected and infected DC will be compared using assays for antigen and mitogen presentation, mixed leukocyte reaction, generation of cytotoxic T cells, and IFN-gamma production. DC of asymptomatic HIV-infected individuals will be characterized with respect to number, HIV infection, and function. The results of these studies will provide new information about these important accessory cells, and will indicate whether HIV infection of DC contributes to immunodeficiency in asymptomatic HIV-infected individuals.
| Chehimi, J; Prakash, K; Shanmugam, V et al. (1993) CD4-independent infection of human peripheral blood dendritic cells with isolates of human immunodeficiency virus type 1. J Gen Virol 74 ( Pt 7):1277-85 |
| Starr, S E; Bandyopadhyay, S; Shanmugam, V et al. (1993) Morphological and functional differences between HLA-DR+ peripheral blood dendritic cells and HLA-DR+ IFN-alpha producing cells. Adv Exp Med Biol 329:173-8 |
| Chehimi, J; Prakash, K; Shanmugam, V et al. (1993) In-vitro infection of peripheral blood dendritic cells with human immunodeficiency virus-1 causes impairment of accessory functions. Adv Exp Med Biol 329:521-6 |
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