Induction of proliferative and destructive graft-versus-host reactions in the small intestine

Abstract

We have used the intestinal phase of a GvHR to investigate the immunological basis of enteropathies associated with CMI. The nature of the damage depends on the model of GvHR used. Adult unirradiated (CBAxBALB/cF1) mice with GvHR developed an entirely proliferative enteropathy characterized by crypt hyperplasia, increased numbers of IEL and enhanced NK cell activity, but there was no villus atrophy or CTL. Although neonatal or irradiated adult (CBAxBALB/c)F1 mice with GvHR developed a destructive enteropathy with marked villus atrophy and CTL activity, this also required an early proliferative phase identical to that found in unirradiated adult mice. Thus, we propose that proliferative enteropathy in GvHR is due to soluble mediators released by a local DTH reaction but that villus atrophy also requires activation of a further population of effector cells, which may be CTL or suppressor T cells.