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Session 44 Poster Session DC-SIGN and Dendritic Cells Session Time: 4:30-6:30 pm Room 4E-F

255-T. Impaired Function of Isolated Blood Myeloid and Plasmacytoid Dendritic Cells from HIV-1-Infected Patients H. Donaghy*1, B. Gazzard2, F. Gotch1, and S. Patterson1 1Imperial Coll. of Sci., Technology, and Med.; and 2Chelsea and Westminster Hosp., London, UK Background: Dendritic cells (DC) are antigen presenting cells that are important in bridging innate and acquired immune responses. In the blood there are at least 2 populations, termed myeloid (myDC) and plasmacytoid (pcDC) DC, which are CD11c+ and CD11c- respectively. myDC are classical antigen presenting cells that migrate from the blood to the tissues whereas pcDC migrate from the blood to the secondary lymphoid organs where they are thought to play a role in tolerance. The concentration of both these populations was progressively reduced with increasing viral load in HIV-1-infected patients. We have investigated whether the function of DC populations from the blood was altered in HIV-1+ patients. Methods: Using a novel technique we have obtained highly purified populations of pcDC and myDC from 50 mL of HIV-1 patient blood with no evidence of T-cell contamination. The function of the DC was assessed by their ability to stimulate allogeneic T-cell proliferation in a mixed leukocyte reaction over 6 days. Thymidine incorporation for the last 16 hours was measured. In addition the HIV-1 pro-virus in pcDC and myDC was assessed by PCR and compared to that found in the T cells of patients. Results: In healthy controls the pcDC showed lower capacity to stimulate naïve allogeneic T cells than the myDC. In treatment naïve HIV-1+ patients with high HIV-1 viral loads the function of both populations of DC studied was found to be impaired. There was a more profound loss of function of the pcDC than the myeloid DC. HIV-1 pro-virus was detected in both populations of purified DC by PCR. Conclusions: Both the myDC and pcDC were functionally impaired in HIV-1 infection however the function of the pcDC was more profoundly affected than the myDC. As pcDC are known to produce the antiviral agent interferon alpha a reduction in the function of these cells may impair the ability of the innate immune system to clear the virus whereas an impairment in the myDC may result in reduced production of HIV-1-specific cytotoxic T lymphocytes. Evidence that the DC are infected with HIV-1 has implications in the pathogenesis of the disease.

©2002 9th Conference on Retroviruses and Opportunistic Infections