Abstract
Requirements for generation of allospecific human CTL [cytotoxic T lymphocytes] in vitro were studied by 3 cell experiments with 2 allogeneic T cell suspensions as coculatured responders, stimulated by irradiated B cells. Enhancement and inhibition of the response are described, with a functional definition of T amplifier and T depressor cells regulating the differentiation of CTL. Enhancement is the result of an amplifying effect on cytotoxic precursor T cells. Amplification is due to the HLA-D region incompatibility between the responding T cell donor and the stimulating donor resulting in strong proliferation. Inhibition is the result of a depressing effect on cytotoxic precursor T cells mediated by cocultured T cells. The depression seems to be due to HLA-A,-B,-D identity between 1 of the responder T cell donors and the stimulator cells. Induction of depression is radiosensitive, accompanied by strong proliferation and CTL generation with cytotoxic specificity against the cocultured and depressed donor target cells. Functionally defined T depressor cells are possibly cytotoxic precursors mediating cytostatic functions before strong cytotoxicity is detectable.