Studies on induction and effector functions of concanavalin A-induced suppressor cells that limit TCGF production.

Abstract

The cellular mechanisms regulating TCGF production in Con A-stimulated cultures have been investigated. Normal spleen cells, activated by Con A for 24 hr, develop suppressive cells that inhibit de novo production of TCGF by fresh spleen cells. Effector cells mediating suppression are nonadherent, radioresistant, Lyt-2-positive T cells. The induction of suppressor cells is radiosensitive and it requires 18 hr. The kinetics of suppressor cell induction parallels very closely the termination of TCGF production in situ, suggesting the major importance of this mechanism in the control of TCGF production. Reculture of 24-hr Con A-activated cells in the absence of Con A for 24 to 72 hr results in a gradual loss of suppressive activity that can be recalled by readdition of Con A with the same kinetics found in fresh spleen cells. In addition, de novo production of TCGF is readily induced in such cultures upon restimulation with Con A, demonstrating that abrogation of TCGF-production in primary cultures is due to suppression and not to lectin-dependent killing of the TCGF-producing T cells. Measurements of suppressive activity and lectin-dependent cytotoxicity, in various populations of Con A-activated spleen cells, further distinguish these activities. Finally, the reduced suppressive activity of Con A-activated cells after expansion in TCGF excludes that suppressor cells act by absorption or removal of TCGF produced at normal rates. Direct, reversible suppression of TCGF-producing cells by T lymphocytes appears, therefore, to constitute a major mechanism by which cytotoxic T cell responses are regulated.