Insulitis as a consequence of immune dysregulation: further evidence

Lymphocytic infiltrations in pancreatic islets (insulitis) have been shown previously to occur in mice with spontaneous or experimentally induced immune disorders. We now have studied which type of immune dysregulation leads to insulitis. Immune disorders were induced by treatment with cyclophosphamide (Cy) or phenytoin and by graft versus host reactions (GVHR) across minor or major histocompatibility barriers. Histological analysis of immune disturbed animals revealed insulitis after phenytoin treatment and as a consequence of GVHR. Insulitis during GVHR is only observed in certain mouse strain combinations. Treatment with Cy in a large dose range does not lead to lymphocytic infiltration of pancreatic islets. It is concluded that cellular immunity to islet cells can occur spontaneously during certain types of immune dysregulation. Since phenytoin treatment and GVHR stimulate lymphocytes reactive with major histocompatibility antigens, such structures may also be part of target antigens on islet cells.