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The Journal of Immunology, 1998, 160: 3673-3680.
Copyright © 1998 by The American Association of Immunologists

CD8+ Cells Are Not Necessary for Allograft Rejection or the Induction of Apoptosis in an Experimental Model of Small Intestinal Transplantation1

Sheri M. Krams2,*,{dagger}, Michihiro Hayashi*, Christine K. Fox*, Janeth C. Villanueva*, Karen J. Whitmer*, Washington Burns{ddagger}, Carlos O. Esquivel* and Olivia M. Martinez*

* Transplant Immunobiology Laboratory, Department of Surgery and {dagger} Digestive Disease Center, Stanford University School of Medicine, Stanford, CA 94305; and {ddagger} California Pacific Medical Center, San Francisco, CA 94115

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.




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[Abstract] [Full Text]


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