INFECTION OF HUMAN MONOCYTES WITH HIV-1BA-L - EFFECT ON ACCESSORY CELL-FUNCTION FOR T-CELL PROLIFERATION INVITRO

Major laboratory manifestations of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) include altered levels of circulating CD4+ lymphocytes and decreased in vitro T-cell mitogenic responses. Since T-cell proliferation is regulated by monocytes (M-phi), studies were undertaken to determine whether defective M-phi function contributes to these poor mitogenic responses. M-phi were isolated from peripheral blood mononuclear cells (PBMC) of normal donors by adherence to plastic. After 5 days in culture, the adherent cells were inoculated with the HIV-1 M-phi-tropic strain, Ba-L. Under these conditions HIV infection in M-phi can be detected 5-7 days after inoculation. Ten to fourteen days postinoculation, the adherent cells were harvested with lidocaine and cocultured with fresh autologous T cells and T-cell mitogens in 3-day assay. We found decreased proliferative anti-CD3 responses to Leu4 and OKT3 and variable responses to concanavalin A (Con A) by T cells cultured with HIV-infected monocytes compared with T cells cultured with uninfected M-phi. Supernatants from HIV-infected M-phi cultures decreased proliferative responses of normal PBMC to anti-CD3 monoclonal antibodies. Heat-activated supernatants had the same effect. Inhibitors of HIV binding did not restore proliferative responses of HIV-infected cultures to normal levels. These results indicate that HIV infection of M-phi causes the release of soluble factor(s) that suppress anti-CD3-induced T-cell proliferative responses.