Dysregulation of cytokines during graft-versus-host disease.

Graft-versus-host disease (GVHD) remains a major complication following allogeneic stem cell transplantation. It is mediated by alloreactive donor T cells recognizing histocompatibility antigens of the host, and ex vivo depletion of these cells from the graft has been used as prophylaxis. This, however, carries increased risk of graft rejection, disease relapse, and impaired immune reconstitution. It now appears that GVHD may be primarily mediated by cytokines. A three-step hypothesis for the involvement of cytokines in the pathophysiology of acute and chronic GVHD is presented, with emphasis on the role of Th1 and Th2 T cell subsets.