Redefining 'self': the role of microflora (commensals) mismatch in the development of GvHD after allogeneic stem cell transplantation and some possible remedies

The discovery of human leukocyte antigen (HLA) molecules and their role in allorecognition has facilitated the initiation of allogeneic stem cell tran splantation in human beings. HLA mismatch to a large extent explains the ph enomenon of graft rejection and graft versus host disease (GVHD). incidence of GvHD even in syngeneic transplants suggests a role for extra genetic fa ctors in the causation of GvHD. We hereby propose a hypothesis that the def inition of 'self' (in the immunological sense) should be broadened to inclu de both genetically determined molecules (e.g. HLA) and the microbial flora that colonize an individual. This hypothesis explains several observations about GvHD which can not fully be accounted for by the HLA mismatch theory and gives some clues towards circumventing GvHD. (C) 2001 Harcourt Publish ers Ltd.