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 semi-allogenic graft-versus-host disease (GvH) are characterized by lymphocytic infiltrates, crypt hyperplasia, and villous atrophy. In the present study, the role of CD40L (gp39)—an important member of the TNF/NGF superfamily of receptors and their ligands—for T-cell costimulationin vivoduring the development of mucosal atrophy was investigated. We found that the inhibition of the CD40L–CD40 interaction in GvH animals by the administration of an anti-CD40L antibody (MR-1) completely prevents the development of crypt hyperplasia and villous atrophy in GvH animals. This includes a normalization of the rate of crypt cell apoptosis, which is augmented in untreated GvH animals. In conclusion, the CD40L–CD40 interaction is crucial in the pathogenesis of T-cell-mediated mucosal atrophy.