Humoral-mediated suppression of interleukin 2-dependent target cell proliferation in acquired immune deficiency...

Sera from patients with acquired immune deficiency syndrome (AIDS) were analysed for effects on normal lymphocyte interleukin 2 (IL-2) production, IL-2 receptor (IL-2R) expression and levels of IL-2 dependent T cell proliferation. The presence of AIDS serum appeared to reduce significantly IL-2 production by cultures of mitogen-activated normal human peripheral blood mononuclear cells (PBMC). However, dilution analyses of the culture supernatants indicated that the primary inhibitory effect occurred at the level of the IL-2 responsive target cell. Furthermore, eight of nine AIDS sera, but none of the normal human sera (NHS) tested, suppressed the capacity of IL-2-dependent CTL-20 cells to proliferate in response to human IL-2. Fractionation of AIDS sera by gel filtration on Sephacryl S-200 revealed that inhibitory activity coeluted with the immunoglobulin fraction. Pretreatment of human IL-2R+ lymphoblasts with AIDS serum did not interfere with the binding of monoclonal antibody (anti-Tac) specific for the human IL-2R; however, significant reductions in the levels of phytohaemagglutinin-induced IL-2R expression were observed when normal human PBMC were cultured in the presence of AIDS serum. These findings indicate that the inhibitor present in many AIDS sera does not suppress lymphocyte proliferation by interfering directly with the IL-2 receptor, and suggest that inhibition occurs at a later stage of the cell cycle. One of the primary consequences of the activity of this serum inhibitory factor is a decline in the levels of lymphocytic IL-2R expression.