The multifactorial etiology of graft-versus-host disease

Graft-versus-host disease (GVHD), a major complication of bone marrow transplantation, often occurs despite genotypic HLA identity between patient and donor. Here, Gijsbert de Gast and his colleagues suggest that pretransplant cytoreductive therapy reactives latent virus and protozoan infections and promotes the invasion of bacteria and fungi through damaged mucosal membranes. Mature donor T cells sensitized to microbial antigens produce gamma interferon that induces the expression of HLA class II antigens. Non-HLA antigens are presented in conjunction with HLA class II antigens and stimulate graft-versus-host reactions against non-HLA antigens expressed on the target cells.