Signal transduction defect in the acquired immunodeficiency syndrome and AIDS-related complex.

Abstract

Peripheral blood mononuclear cells from patients with the acquired immunodeficiency syndrome (AIDS), AIDS-related complex (ARC), and heterosexual controls were stimulated with anti-CD3 monoclonal antibody, phorbol myristate acetate (PMA), or both and 3H thymidine incorporation and IL-2 receptor (IL-2R alpha; CD25; Tac antigen) expression were measured. In addition, basal plasma membrane potential and plasma membrane potential following anti-CD3 stimulation were compared between the three groups. A significantly reduced DNA synthesis and CD25 expression was observed in both AIDS and ARC upon stimulation with anti-CD3 or PMA. Although, a significant synergism was observed with anti-CD3 plus PMA stimulation in both AIDS and ARC, and the responses were normalized to the levels of anti-CD3 or PMA response in normal control, the levels were significantly lower than those observed with anti-CD3 plus PMA in controls. Plasma membrane potentials were decreased (membrane depolarized) in both ARC and AIDS (AIDS > ARC), and anti-CD3 had no effect on further depolarization of plasma membrane in AIDS. These data suggest a defect in signal transduction pathway in patients with HIV-1 infection.