Significant inhibition of human CD8(+) cytotoxic T lymphocyte-mediated xenocytotoxicity by overexpression of the human decoy Fas antigen

Transplantation
K KawamotoHikaru Matsuda

Abstract

Human CD8(+) CTL-mediated killing may be important for xenograft rejection. The purpose of this study was to explore the preventing methods for CTL-mediated xenocytotoxicity by overexpression of human decoy Fas, which lacks a death domain in its cytoplasmic region, by binding competition with endogenous pig Fas. Moreover, the cytoprotective effect of this CTL-killing of membrane-bound human FasL, which is resistant to metalloproteolytic cleavage, was also assessed. Human CTL were generated by the stimulation of human PBMC with swine endothelial cells (SEC) and human IL-2, subsequently a CD8(+) population were selected by magnetic beads and employed as the effector cells. Stable SEC transfectants expressing either decoy Fas or membrane-bound FasL were established. Double-transfectants were also created. The amelioration of cytotoxicity to these transfectants was examined with Cr release assay. RESULTS.: Human CD8(+) CTL were highly detrimental against parental SEC. This CTL-killing was strongly inhibited by anti-FasL mAb treatment, however partial suppression was observed by Concanamycin A treatment. The overexpression of either decoy Fas or membrane-bound FasL in SEC markedly inhibited CTL-xenocytotoxicity. The double expressio...Continue Reading

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Citations

Jan 24, 2008·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·M TanemuraT Ito
Nov 17, 2019·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Rabea HeinReinhard Schwinzer
Nov 20, 2016·Xenotransplantation·Natacha MadelonJörg D Seebach

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