Revisiting graft-versus-host disease models of autoimmunity: new insights in immune regulatory processes.

Graft-versus-host disease (GVHD) commonly occurs when immunocompetent donor cells attack a genetically disparate host. GVHD occurs primarily after allogeneic bone marrow transplantation (BMT) and remains a significant cause of morbidity, thus limiting the efficacy of this treatment. GVHD can exist as two distinct clinical entities: acute (affecting multiple solid organs) and chronic (presenting with solid organ pathology but also with autoimmune-like sequelae) (1, 2). New means to reduce the toxicity but retain the antitumor potential of BMT include donor lymphocyte infusions, nonmyeloablative conditioning, and the use of G-CSF to mobilize peripheral blood stem cells, all of which have led to significant reductions in the occurrence of acute GVHD (1). Unfortunately, with the decline of acute GVHD, chronic GVHD is emerging as a dominant complication in BMT (1, 2). Researchers examining GVHD have used numerous model systems, which has often resulted in confusion in extrapolating results from one model to another. GVHD models differ from one another with respect to three key features: the extent and type of conditioning or cytoreductive treatment of the recipient using total body irradiation or chemotherapy; the extent of genetic disparity between donor and host; and the purity, type, and number of donor cells transferred. These three variables have a dramatic impact on the type and extent of the resulting GVHD.