These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Preventing human CD8+ cytotoxic T lymphocyte-mediated cytotoxicity against swine endothelial cells by overexpression of human decoy Fas antigen.
    Author: Kawamoto K, Tanemura M, Ito T, Uchikoshi F, Shimada K, Nishida T, Matsuda H.
    Journal: Transplant Proc; 2005; 37(1):500-2. PubMed ID: 15808689.
    Abstract:
    Although the birth of homozygous alpha1, 3 galactosyltransferase gene-knockout pigs raised hopes for an imminent breakthrough in the prevention in the antibody-mediated rejection of pig to human discordant xenotransplants, human CD8(+) cytotoxic T lymphocyte (CTL)-mediated killing may represent a new immunological barrier to long-term survival in xenograft recipients. In this study, we demonstrated that the cytotoxicity of human CD8(+) CTL against swine endothelial cells (SEC) is highly detrimental and mediated at least in part by the Fas/FasL pathway. To prevent this CTL-mediated xenocytotoxicity, we overexpressed the human decoy Fas antigen, which does not contain a death domain in its cytoplasmic region, by means of binding competition with endogenous pig Fas antigen on SEC for the common ligand, human FasL. Furthermore, we generated a membrane-bound form of human FasL that cannot be cleaved by a putative metalloproteinase to produce a soluble form, which was assessed as an inhibitor of CTL cytotoxicity. Both human decoy Fas and membrane-bound FasL were effective to prevent CTL-mediated killing, suggesting that these novel molecules may represent a step forward toward preventing CD8(+) CTL-mediated xenograft rejection. The combined expression of both molecules may be more beneficial to protect xenograft cells.
    [Abstract] [Full Text] [Related] [New Search]