Graft-versus-host reactions in the rat mimic toxin-induced autoimmunity

Gold salts, D-penicillamine or mercurials induce autoimmunity in Brown Norway (BN) rats and provoke an immunosuppression in Lewis (LEW) rats. It has been suggested that immunologically mediated manifestations induced by drugs could result from graft-versus-host (GVH) like reactions. We show that BN spleen cells transferred into (LEW x BN)F1 hybrids induce a chronic GVH reaction (GVHR). This reaction led to an autoimmune disease quite similar to that induced by drugs in BN rats. In both situations, a common part of the B cell repertoire is triggered. In contrast, LEW spleen cells transferred into (LEW x BN)F1 hybrids provoke a lethal GVHR. This is to be compared with the CD8-mediated immunosuppression observed in LEW rats injected with HgCl2. These findings are in agreement with the prediction that immune dysregulation induced by drugs leads to GVH-like reactions either stimulatory or suppressive depending upon the strain tested.