Regulation of in vitro cytotoxic T lymphocyte generation. I. Evidence that killer cell precursors differentiate to effector cells in two steps

The differentiation of cytotoxic T lymphocyte precursor cells (CTL-P) into CTL effector cells is a two-step process. In the first step, naive CTL-P (CTL-PN) become activated (CTL-PA) but do not yet have the capacity to kill target cells. CTL-PA can be distinguished from CTL-PN because the former are far less sensitive than the latter to the effects of in vitro-generated suppressor cells. Thus, the addition of suppressor T cells (Ts) to a fresh MLC can totally inhibit the production of CTL from CTL-PN, whereas the same Ts only minimally affect the generation of CTL from CTL-PA. It is not known whether these Ts act directly on CTL-PN or on a helper cell needed for activation to CTL-PA. The production of CTL-PA can take place in allogeneic mixed leukocyte cultures (MLC) treated with the drug pyrilamine, or when heat- inactivated stimulator cells are used. Each of these treatments inhibits the differentiation of CTL-PA to CTL. However, if pyrilamine is removed, a nonspecific MLC-derived signal can induce these CTL-PA to become CTL, even in the presence of significant numbers of Ts. This two step process of differentiation of CTL-P to CTL may be analogous to the way naive B cells become antibody-producing cells.