Approaches to graft-vs-host disease.

Graft-vs-host disease (GVHD) is one of the most difficult problems in stem cell transplantation. It is best considered in the context of the normal immune response. The role of the immune system is to identify and eliminate foreign antigens. In the case of GVHD, the antigens are minor histocompatibility antigens (mHA) recognized in an inflammatory milieu. The immune system cannot reasonably be expected to selectively recognize microbial antigens and ignore mHA. This approach would require the generation of selective tolerance--something that clearly occurs but which we have frustratingly little control over. While we can often treat and remit even life-threatening GVHD, the consequence has been the development of fatal opportunistic infections. The challenge is to change our style of thinking about GVHD to allow a transition from a 'nuclear winter' approach that controls GVHD at the price of infection, to a more selective patient approach that recognizes the limitations of immunosuppressive therapy.