Dendritic cells in HIV-1 and HTLV-1 infection

Individuals with HIV-1 infection show two major immunological effects--the early persistent stimulation of immune responses (e.g. of CD8 cells and antibody production) and later catastrophic immunodeficiency. Peripheral blood dendritic cells (DC) become infected with HIV-1 and infected cells can stimulate responses to virus. By contrast infected DC show a reduced capacity to stimulate either primary or secondary responses to other antigens. We have proposed that the block, particularly in primary responses, may be instrumental in the development of immunodeficiency. In HTLV-1 infected patients with tropical spastic paraparesis (TSP) a major feature of disease is 'spontaneous' T cell proliferation thought to underlie development of inflammatory neurological disease. We have now shown that some DC in addition to T cells are infected in TSP and that DC stimulate the persistent T cell activity. Here we demonstrate this using cells from an informative family where the daughter was normal, the father an HTLV-1 seronegative carrier and the mother had TSP. DC from all individuals stimulated normal allogeneic T cells in a mixed leukocyte reaction (MLR) and T cells responded well to normal allogeneic DC. T cells from the daughter showed little stimulation with autologous DC, those from the father showed significant but low stimulation, and T cells from the TSP patient gave a response to autologous DC which exceeded that to allogeneic DC. Taken together, the studies of DC and both HIV-1 and HTLV-1 indicate that infection of DC may play a central role in development of T cell abnormalities in human retrovirus-induced diseases.