Effect of major histocompatibility complex expression on murine intestinal graft survival

Background. Clinical intestinal transplantation has been plagued by frequent and severe graft rejection, It has been proposed that the major histocompatibility complex (MHC) antigens might play a critical role in this process owing to their extensive expression on enterocytes and mucosa-associated immune cells. Methods. The present study examined the role of MHC antigens in intestinal graft rejection using MHC class I-deficient and MHC class II-deficient donors. Results. Grafts with normal MHC expression were rejected by 9 days, whereas survival was prolonged to 14 days in the MHC class II-deficient grafts (P=NS) and to 20 days in the MHC I-deficient grafts (P<0.002). In all groups, early rejection was characterized by (1) increased crypt cell apoptosis, as detected by the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) technique of in situ labeling; and (2) the increased expression ob perforin and a CD8 phenotype in the graft-infiltrating cells. Conclusions. These data suggest that MHC antigens, CDS-positive T cells, and perforin-expressing cells contribute to intestinal graft rejection. Apoptosis of the progenitor epithelial crypt cells during early intestinal rejection may impair the gut's ability to regenerate and repair mucosal damage.