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, naïve 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 naïve B cells become antibody-producing cells.
D000818:Animals; D000954:Antigens, Surface / Q000235:genetics; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006358:Hot Temperature; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D011738:Pyrilamine / Q000494:pharmacology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology; D018800:Thy-1 Antigens; D013997:Time Factors
D000954:Antigens, Surface; D008565:Membrane Proteins; D018800:Thy-1 Antigens; D011738:Pyrilamine