In vivo analysis of allogeneic lymphocyte interaction: activation of suppressor T cells by an I-J-restricted allogeneic effect factor (AEF).

Abstract

The preceding paper detailed the production and fractionation of a T cell-derived I-J-specific allogeneic effect factor (AEF) and analyzed its ability to provide help in a T cell-depleted, in vitro primary anti-sheep erythrocyte response. The identical AEF fractions were examined in this study for their ability to elicit suppression in a delayed-type hypersensitivity assay. Previous reports showed that low or suboptimal doses of antigen, presented i.v. on a cell surface, induce a precursor or primed set of suppressor T cells (pre Ts). These cells manifested antigen-specific suppression only in the presence of a T cell-mediated I-J-specific allogeneic effect induced in vivo against the pre Ts. The experiments reported here examined the ability of alloactivated T cell-derived I-J-specific AEF components to replace the in vivo I-J allogeneic effect. The results show that certain AEF components can indeed provide the signal(s) necessary for activation of suppression. Size and charge separation of the crude AEF preparation revealed several components, some of which could independently serve as appropriate inductive signals. One of these components proved to be biochemically identical to interleukin 2 (IL 2) and accounted for some of the genetically unrestricted AEF activity observed; other higher m.w. molecules also possessed unrestricted activity. Another component provided the requisite activational signals and this 68,000-dalton, pI 5.6 molecule(s) was I-J restricted. These findings are discussed in terms of models of lymphocyte subset interactions and activation.