Effect of major histocompatibility complex expression on murine intestinalgraft survival

Background. Clinical intestinal transplantation has been plagued by frequen t and severe graft rejection, It has been proposed that the major histocomp atibility complex (MHC) antigens might play a critical role in this process owing to their extensive expression on enterocytes and mucosa-associated i mmune 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 dono rs. 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 increa sed expression ob perforin and a CD8 phenotype in the graft-infiltrating ce lls. Conclusions. These data suggest that MHC antigens, CDS-positive T cells, an d perforin-expressing cells contribute to intestinal graft rejection. Apopt osis of the progenitor epithelial crypt cells during early intestinal rejec tion may impair the gut's ability to regenerate and repair mucosal damage.