title: CD8+ cells are not necessary for allograft rejection or the induction of apoptosis in an experimental model of small intestinal transplantation.
abstract: Allospecific CTL can function as cellular effectors of solid organ graft rejection; however, the specific mechanisms of cell damage remain undetermined. In this study we examined the role of CD8+ T cells in apoptosis and rejection of small intestinal allografts. ACI rat intestinal grafts transplanted into Lewis rat recipients showed apoptosis of epithelial crypt cells on day 3 posttransplant as determined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling staining. By day 7 numerous apoptotic crypt cells were detected in allografts, but were rarely observed in FK506-treated allograft recipients, isografts, or native intestine of allograft recipients. To further investigate the mechanism of rejection, recipient rats were depleted of CD8+ cells by treatment with OX-8 mAbs the day before and the day after transplantation of rat small intestinal allografts. Depletion of CD8+ cells from allograft recipients did not alter the tempo or the histologic features of rejection compared with those in the control (IgG-treated) group. Moreover, there was no difference in the number of apoptotic crypt epithelial cells in the grafts of control and CD8-depleted rats. Reverse transcriptase-PCR analyses determined there were similar levels of transcripts for Fas, Fas ligand, perforin, and granzyme B in control and CD8-depleted allograft recipients. By Western blot it was determined that the levels of Fas ligand protein were increased in the CD8-depleted group compared with those in control and FK506-treated allograft recipients. These data suggest that CD8 cells are not required for tissue injury or apoptotic cell death in small intestine allograft rejection.
authors.affiliation: Department of Surgery and Digestive Disease Center, Stanford University School of Medicine, CA 94305-5487, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Krams
authors.forename: M
authors.initials: M
authors.lastname: Hayashi
authors.forename: C K
authors.initials: CK
authors.lastname: Fox
authors.forename: J C
authors.initials: JC
authors.lastname: Villanueva
authors.forename: K J
authors.initials: KJ
authors.lastname: Whitmer
authors.forename: W
authors.initials: W
authors.lastname: Burns
authors.forename: C O
authors.initials: CO
authors.lastname: Esquivel
authors.forename: O M
authors.initials: OM
authors.lastname: Martinez
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D053222:Fas Ligand Protein; D006084:Graft Rejection / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D053804:Granzymes; D007421:Intestine, Small / Q000276:immunology / Q000473:pathology / Q000637:transplantation*; D008212:Lymphocyte Depletion; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D016377:Organ Transplantation; D054353:Perforin; D016133:Polymerase Chain Reaction; D052899:Pore Forming Cytotoxic Proteins; D051381:Rats; D011912:Rats, Inbred ACI; D011917:Rats, Inbred Lew; D012697:Serine Endopeptidases / Q000235:genetics; D014184:Transplantation, Homologous; D019014:fas Receptor / Q000235:genetics
chemical_list: D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D019014:fas Receptor; D054353:Perforin; D053804:Granzymes; C509215:Gzmb protein, rat; D012697:Serine Endopeptidases