Infection of dendritic cells with HIV1: virus load regulates stimulation and suppression of T-cell activity

Patients with HIV infection show two major types of immunological effects. The first is hyperactivity of both T and B lymphocytes which may be in response to HIV antigens themselves, and the second is a loss in T-cell activity in response to other antigens. Dendritic cells (DC) show a higher rate of infection with HIV than other peripheral blood cells in vitro and in vivo. The effects of HIV infection of DC in vitro on their stimulating capacity for T cells were, therefore, examined. We compared the development of the capacity to stimulate primary proliferative responses to virus in autologous lymphocytes with their potency in stimulating allogeneic cells in the mixed leukocyte reaction (MLR). Small numbers of uninfected DC caused little or no stimulation of autologous lymphocytes, but stimulated high MLR. The level of HIV infection in in vitro infected DC preparations was dependent on the time of infection and the titre of the input virus. DC exposed to low doses of HIV (e.g., 10(3) TCID/10(6) cells) for up to 4 days or to a higher dose (e.g. 10(5) TCID/10(6) cells) for 1 day caused significant primary proliferation in autologous T cells and, under these conditions, capacity to stimulate allogeneic MLR remained intact. However, DC exposed to increasing doses of HIV or infected for a longer period showed reduced capacity to stimulate allogeneic lymphocytes and then a loss of stimulation of autologous cells. This provides evidence suggesting that both stimulatory and inhibitory effects of HIV infection can be produced through infection of DC.