Dendritic Cells in HIV-1 and HTLV-1 Infection

Summary

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-l^1-6 and infected cells can stimulate responses to virus⁷. By contrast infected DC show a reduced capacity to stimulate either primary or secondary responses to other antigens^2,3,8. We have proposed that the block, particularly in primary responses, may be instrumental in the development of immunodeficiency^8,9.

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 disease¹⁰. 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 daugther was normal, the father an HTLV-1 seronegative carrier and the mother had TSP. DC from all individuals stimulate 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.