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

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Abstract
The differentiation of mouse cytotoxic T lymphocyte precursor cells (CTL-P) into CTL effector cells is a 2-step process. In the 1st 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 mixed leukocyte culture (MLC) can totally inhibit the production of CTL from CTL-PN; 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 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 2 step process of differentiation of CTL-P to CTL may be analogous to the way naive B cells become antibody-producing cells.

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