IL-2 and IL-4 can co-modulate the generation of cytotoxic T cells through CD8- CD4- splenic lymphocytes

Abstract

Following activation with concanavalin A (Con A), murine T cells are able to suppress the generation of allospecific cytotoxic T lymphocytes (CTL). We have analysed the phenotype, tissue distribution, and mode of action of these cells in an effort to understand further the regulation of CTL-mediated immunity. The precursors of such cells are rare (1 cell per 70,000 spleen cells being able to suppress the generation of a particular allospecific response), but are much more abundant in the spleen than in the thymus. By the use of cytotoxic antibodies, we have been able to demonstrate that the splenic precursors of such cells are Thy-1.2+, CD4-, CD8- but, following activation with Con A, these cells acquire the CD8 marker. Cellular suppression by these lymphocytes is dramatically increased in the presence of the Th2-derived lymphokine, IL-4, whereas IL-2, the Th1-derived lymphokine, significantly augments the generation of CTL in a mixed lymphocyte culture even though relative suppression is still evident in the presence of Con A-activated lymphocytes. Suppression is not due to overcrowding of a cell culture since adding Con A-activated cells to an A anti-B + C culture often resulted in the suppression of the A anti-B response but not the A anti-C response, or vice versa. Suppression appears to require cellular interaction since supernatants from Con A-activated lymphocytes are unable to mediate suppression. Such cells may play an important intermediate role in homeostasis.