A syngeneic MLR induced in vivo results in T-cell mediated immune suppression

The proliferation of murine T lymphocytes in response to syngeneic Ia bearing non-T cells (syngeneic mixed lymphocyte reaction, SMLR) has been shown to generate regulatory T cells in vitro. An in vivo regulatory role has therefore been proposed for the SMLR. To study this role more directly, we examined the effects of repeated iv injection of mice with activated syngeneic B cells. Three such weekly injections induced a suppression of the plaque forming cell response to a subsequent injection of trinitrophenylated keyhole limpet hemocyanin (TNP-KLH). The suppression was transient and could not be maintained by additional injections of activated syngeneic B cells. The suppression was transferable to syngeneic recipients with splenic lymphocytes. Continued weekly iv injections of LPS induced blasts, as well as weekly intraperitoneal injections, caused enhancement rather than inhibition of the response to iv injected TNP-KLH. The enhancement was prevented by injection of anti-L3T4. Spleen cells from mice which had received three iv injections of activated syngeneic cells suppressed an in vitro secondary response to TNP-KLH by normal immune spleen cells. The cells responsible for the immune suppression were Thy 1.2+. The results indicate that repeated exposure to activated B cells causes activation of suppressor pathways but does not bring about a chronic state of immune suppression.