The effect of anti-gp39 treatment on the intestinal manifestations of acute murine graft-versus-host disease

The changes in the intestinal morphology of murine T-cell-mediated acute se mi-allogenic graft-versus-host disease (GvH) are characterized by lymphocyt ic infiltrates, crypt hyperplasia, and villous atrophy. In the present stud y, the role of CD40L (gp39)-an important member of the TNF/NGF superfamily of receptors and their ligands-for T-cell costimulation in vivo during the development of mucosal atrophy was investigated. We found that the inhibiti on of the CD40L-CD40 interaction in GvH animals by the administration of an anti-CD40L antibody (MR-1) completely prevents the development of crypt hy perplasia and villous atrophy in GvH animals. This includes a normalization of the rate of crypt cell apoptosis, which is augmented in untreated GvH a nimals. In conclusion, the CD40L-CD40 interaction is crucial in the pathoge nesis of T-cell-mediated mucosal atrophy, (C) 1999 Academic Press.