Pathophysiology of graft-versus-host disease directed to minor histocompatibility antigens.

Our investigations related to GVHD over the last few years have established the role of CD8+ and CD4+ T cell subsets in the etiology of the disease across different genetic barriers and has raised several important questions about the nature of in vivo functions and mechanisms of pathogenesis of these subsets. Immunodominance in the GVHD response of T cells to multiple minor H antigens seems to play a major role in vivo, and differs from that observed in vitro. Understanding this phenomenon is a high priority if we are to be able to cope with human minor H antigens clinically. Finally, utilizing our working knowledge of T cell subsets and GVHD, we need to know whether selective depletion of donor inoculum and donor pre-sensitization could be advantageous in the clinical situation.