Infection of Human Monocytes with HIV-1 Ba-L . Effect on Accessory Cell Function for T-Cell Proliferation In Vitro

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 (Mø), studies were undertaken to determine whether defective Mø function contributes to these poor mitogenic responses. Mø 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 Mø-tropic strain, Ba-L. Under these conditions HIV infection in Mø 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 a 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 Mø. Supernatants from HIV-infected Mø 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 Mø causes the release of soluble factor(s) that suppress anti-CD3-induced T-cell proliferative responses.