Infection of human monocytes with HIV-1Ba-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 (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 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 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.
Melendez-Guerrero
L M
LM
Department of Pathology, Emory University School of Medicine, Atlanta, GA.
Nicholson
J K
JK
McDougal
J S
JS
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000382:microbiology; D002478:Cells, Cultured; D015497:HIV-1 / Q000254:growth & development / Q000302:isolation & purification*; D006801:Humans; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D009000:Monocytes / Q000382:microbiology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000382:microbiology