Suppressor-target interaction in alloantigen induced responses: induction of a second cell in the suppressive pathway

The sequence of events involved in MLR-TsF-induced suppression of the mixed lymphocyte response has been investigated. It is demonstrated in this report that MLR-TsF, which is secreted by predominantly Ly-2+ alloantigen-primed splenic T cells, carries out its suppressive function through the active recruitment of an intermediary suppressor cell. Substantial suppression of the proliferative response is observed when unprimed BALB/c splenocytes are cultured with MLR-TsF and then added as irradiated regulator cells to MLR. This inductive process is dependent on factor concentration, requires a 48-hr exposure of cells to MLR-TsF, and occurs in the absence of added priming strain alloantigen. The target cell involved in this factor-cell interaction is characterized as a nonadherent, Ly-1+2+ T cell resistant to complement-dependent cytotoxicity with a monoclonal anti-Thy-1.2 antibody. In addition, second-order suppression does not appear to operate in an antigen-specific manner. These studies indicate that MLR suppression is a complex process involving a series of interactions between cellular components and their soluble regulatory products.