Decreased accessory cell function of macrophages after infection with human immunodeficiency virus type 1 in vitro

Peripheral blood monocytes from human immunodeficiency virus (HIV)-infected individuals or AIDS-related complex/AIDS patients ex vivo exhibit distinct alterations in some but not all immune functions. In studies presented here, monocytes from healthy donors were infected with HIV 1 in vitro and co-cultures with autologous uninfected T lymphocytes were set up. The monocyte/macrophage (M phi)-dependent T cell function was determined by measurement of proliferative and secretory interleukin (IL)2, interferon-gamma] responses to lectin (phytohemagglutinin), mitogen (anti-CD3 monoclonal antibody), or recall antigen (tetanus toxoid, tuberculin). Accessory function of M phi was normal after HIV infection when optimal amounts (10%-20%) were added to the T lymphocytes. However, HIV infection of M phi significantly decreased T cell proliferative responses and secretion of IL2 when supplemented at limited dilution (0.5%-5%), although interferon-gamma production was not affected. Whereas the lipopolysaccharide-triggered M phi production of IL1 was not impaired by HIV 1 infection, there was a significant decrease in this response when anti-CD3 monoclonal antibody or tetanus toxoid were used to trigger the peripheral blood mononuclear cells. The impairment of proliferation of T lymphocytes in the presence of HIV 1-infected M phi could be overcome by addition of exogenous IL 1. Taken together, these data clearly show that the mononuclear phagocyte-dependent enhancement of stimulated T cell proliferation and lymphokine secretion is decreased when the restricted numbers of monocytes/M phi are HIV 1 infected. There are, therefore, two possible roles of M phi in HIV infection and progression to disease. First, as a reservoir and vehicle for dissemination of the virus, and second, as an immune cell whose essential functions are impaired by infection.