Relative efficiency of porcine and human cytotoxic T-lymphocyte antigen 4 immunoglobulin in inhibiting human CD4+ T-cell responses co-stimulated by porcine and human B7 molecules.

作者: Tadatsura Koshika , Carol Phelps , Jason Fang , Seung Eun Lee , Minoru Fujita

DOI: 10.1111/J.1365-2567.2011.03496.X

关键词: AntigenCytotoxic T cellCellBiologyTransplantationXenotransplantationPeripheral blood mononuclear cellAntibodyMolecular biologyCytotoxicity

摘要: α1,3-Galactosyltransferase gene-knockout pigs transgenic for porcine cytotoxic T-lymphocyte antigen 4 immunoglobulin (pCTLA4-Ig) have been produced to reduce T-cell-mediated rejection following xenotransplantation. The level of soluble pCTLA4-Ig in their blood was greatly excess the therapeutic patients, rendering immune-incompetent. Soluble by these evaluated binding and human (h) B7 molecules, its inhibitory effect on allogeneic xenogeneic T-cell responses. Porcine CTLA4-Ig-expressing peripheral mononuclear cells (PBMCs) aortic endothelial (AECs) were direct hCD4+ purified hCTLA4-Ig showed similar pB7 but significantly less hB7 molecules. inhibited response T pAECs equally, successful inhibiting response. PBMCs from lower than that non-pCTLA4-Ig pigs. Although detected cytoplasm pCTLA4-Ig-expressing pAECs, only a minimal supernatant during culture, did not inhibit High-level tissue-specific production may be required sufficient immunosuppression organ or cell (e.g., islets) transplantation.

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