Effect of anti-CD3/anti-CD28/interleukin-2 stimulation of mononuclear cells on transforming growth factor beta inhibition of lymphokine-activated killer cell generation.

After simultaneous stimulation with anti-CD3 monoclonal antibody (mAb) at 10 ng/ml, anti-CD28 mAb at 125 ng/ml, and interleukin-2 (IL-2) at 20 U/ml, peripheral blood mononuclear cells (PBMC) were partially resistant to immunosuppression by transforming growth factor-beta (TGF beta 2). The doses of TGF beta 2 that inhibit cytotoxicity of IL-2 stimulated cells by 60%-70% were much less effective when the same cells were stimulated with anti-CD3/anti-CD28/IL-2. This favorable stimulation a generated a cell population characterized by high lytic activity, excellent expansion, and a greater resistance to immunosuppressive action of TGF beta 2. The secretion of secondary cytokines important for LAK generation is considered a crucial event, at least partially responsible for the antagonization of TGF beta immunosuppression.