CD8+ Cells Are Not Necessary for Allograft Rejection or the Induction of Apoptosis in an Experimental Model of Small Intestinal Transplantation

• Published in: The Journal of immunology (1950) 1998-04, Vol.160 (8), p.3673-3680
• Main Authors: Krams, Sheri M, Hayashi, Michihiro, Fox, Christine K, Villanueva, Janeth C, Whitmer, Karen J, Burns, Washington, Esquivel, Carlos O, Martinez, Olivia M
• Format: Article
• Language: English
• Subjects: AIDS/HIV; Animals; Apoptosis - immunology; CD8-Positive T-Lymphocytes - immunology; Fas Ligand Protein; fas Receptor - genetics; Graft Rejection - etiology; Graft Rejection - immunology; Graft Rejection - pathology; Granzymes; Intestine, Small - immunology; Intestine, Small - pathology; Intestine, Small - transplantation; Lymphocyte Depletion; Male; Membrane Glycoproteins - genetics; Organ Transplantation; Perforin; Polymerase Chain Reaction; Pore Forming Cytotoxic Proteins; Rats; Rats, Inbred ACI; Rats, Inbred Lew; Serine Endopeptidases - genetics; Transplantation, Homologous
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.160.8.3673

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.