Suppression of immune responses by dendritic cells infected with HIV.

Evidence of human immunodeficiency virus (HIV) replication both in the skin Langerhans' cells of AIDS patients (Tschachler et al., 1987) and in normal, peripheral blood dendritic cells (DC) (Patterson & Knight, 1987; Knight & Patterson, 1989) suggests that infection of these antigen-presenting cells may contribute to the immunosuppression seen in AIDS. Support for this hypothesis is now provided by experiments in which the capacity of DC infected in vitro to present mitogen to normal syngeneic lymphocytes was measured. Infecting DC with HIV before culturing with lymphocytes inhibited mitogen-stimulated cell proliferation. Viral DNA was detected in DC in these cultures by in situ hybridization but, in addition, HIV was also present in a small proportion of lymphocytes. However, introducing an inhibitor of virus replication, 2',3' dideoxyadenosine, after infection of the DC but before culturing with lymphocytes, blocked growth of HIV in lymphocytes. In these latter experiments mitogen proliferation responses were still suppressed. Infection of DC could, therefore, cause immunosuppression in AIDS, both by direct effect on antigen-presentation and by the transfer of HIV to T cells.