ROLE OF DENDRITIC CELLS IN T-CELL PRIMING AND HIV INFECTION
Transmission of HIV is likely to be facilitated by the interaction of the virus with dendritic cells (DCs), which are abundant at mucosal surfaces and traffic to draining lymph nodes. We have shown that after HIV binds to DCs, through a specific interaction of the viral envelope glycoprotein with the C-type lectin DC-SIGN, viral infectivity is dramatically enhanced. This enhanced infectivity requires the internalization of HIV into a specialized recycling vesicular compartment. We are examining the mechanism by which viral internalization results in increased infectivity of target T cells.
To study the function of DCs in vivo, we have prepared transgenic mice whose DCs express diphtheria toxin receptor, allowing their specific elimination within hours after treatment with diphtheria toxin. Studies with these mice have demonstrated that responses of naïve CD8+ T cells against cell-associated antigen or pathogens such as Listeria and the malaria parasite require the presence of DCs. This model will be used to validate the importance of DCs in infection of the host with HIV.
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