Generation of effector cells from T cell subsets. II. Lyt 123 T cells contain the precursors for all primary cytotoxic effector cells and for cells involved in the regulation of cytotoxic responses.

Abstract

Mixed responder populations, consisting of selected Lyt-2,3+ cells and unselected T cells from two congenic mouse strains differing in their Lyt-2,3 alleles, were used to study the role of Lyt-1,2,3+ cells in the generation of cytotoxic effector cells in vitro. The fact that, under these conditions, all primary alloreactive and H-2-restricted killer cells ar generated from the unselected T cell population and not from the selected Lyt-2,3+ subset is demonstrated. Isolated, unsensitized Lyt-2,3+ cells are able to produce primary alloreactive cytotoxic T lymphocytes (CTL) when incubated with alloantigen alone, but appear to be suppressed in the pesence of Lyt-1,2,3+ cells. In contrast, mixtures of Lyt-2,3+ cells selected from C57BL/6 T cells previously primed to alloantigen in vitro, and unselected T cells from the Lyt-2,3-congenic partner after exposure to the same antigen give rise to cytotoxic effector cells which derive mainly from the primed Lyt-2,3+ cell pool and not from the unselected T cell population. Both populations were able to generate CTL when sensitized separately with the alloantigen. The data suggest that Lyt-1,2,3+ cells contain all primary precursors for both H-2 restricted and alloreactive killer cells, as well as lymphocytes suppressing the formation of cytotoxic effector cells from unsensitized Lyt-2,3+ cells. The Lyt-2,3+ cell pool most likely contains the secondary CTL precursors. In addition, the same antigen-primed Lyt-2,3+ pool contains suppressor cells which inhibit the formation of primary CTL from Lyt-1,2,3+ cells. The data are discussed with respect to the regulation of cytotoxic responses.