Down-regulation of adoptive adjuvant-induced arthritis by suppressor factor(s).

We recently described a method for inducing immunologic tolerance to trinitrochlorobenzene (TNCB), a hapten that generates suppressor cells capable of down-regulating the efferent phase of TNP-specific contact hypersensitivity in rats. Peritoneal exudate cells (PEC) of such tolerized rats, upon being triggered by specific hapten, suppressed contact hypersensitivity to another hapten elicited at the same time. This implied that cells that mediate delayed-type hypersensitivity of any specificity might be down-regulated, provided that the suppressor cells are activated with specific antigen and that the unrelated delayed-type hypersensitivity is elicited in parallel. To rigorously test this possibility, we examined the ability of TNP-specific suppressor lymphoid cell factors to affect cells that mediate adoptively transferable adjuvant-induced arthritis (AIA) in rats. To induce arthritis, spleen cells from Freund's complete adjuvant-injected rats were stimulated with concanavalin A and administered to naive recipients. Prior to adoptive transfer, the cells were exposed for brief intervals to supernatants of lymphoid cells from control and hapten-tolerized rats. Supernatants of PEC and lymph node cells from hapten-tolerized rats were found to markedly reduce the effectiveness of cells that mediate AIA. The hapten-tolerized cells required reexposure to hapten prior to preparation of the supernatants. Supernatants of spleen cells from hapten-tolerized rats that had been hapten-painted as well as hapten-triggered and supernatants of lymph node cells and of PEC from only hapten-painted or hapten-triggered rats were ineffective in altering the AIA. Thus, factors from suppressor cells induced toward hapten-coupled self-antigens have been found to adversely affect the function of lymphoid cells that mediate a totally unrelated inflammatory response, namely, AIA. The clinical implications of these findings are discussed.