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• W2012143342 endingPage "1982" @default.
• W2012143342 startingPage "1974" @default.
• W2012143342 abstract "In vitro, soluble MHC (sMHC) antigens modulate and induce apoptosis in alloreactive and antigen-specific T cells, demonstrating their potency to regulate T cell-mediated immune responses. However, their efficacy to regulate immunological responses in vivo remains unclear. Here, we report that repetitive intraperitoneal injection of recombinant Lewis rat-derived MHC class I antigens in Dark Agouti (DA) rats modulates alloreactivity.RT1.A1 (Lewis derived) genes were cloned into mammalian expression vectors, and RT1.Aa (DA derived) genes were used to transfect a rat myeloma cell line. RT1.A1 molecules were injected intraperitoneally in DA recipients that subsequently underwent transplantation with Lewis-derived cardiac allografts.Soluble class I antigens were secreted by the transfected cells and were shown to be heterodimeric, peptide-loaded, and conformationally folded. Injection of donor-derived soluble MHC significantly reduced the ability of recipient animals to mount a cytotoxic T-cell response to donor-derived tissue. More interestingly, this treatment significantly prolonged donor-graft survival and allowed 60% of treated animals to develop graft tolerance (>120 days), when donor sMHC were combined with a single subtherapeutic dosage of cyclosporine. Thymectomy of recipient animals before transplantation did not interfere with induction of peripheral tolerance.Donor-derived sMHC are potential tolerogens for down-regulating the cytotoxic T-cell response of animals that undergo transplantation. Thus, these data provide for the first time a rationale for the application of directly injected sMHC in vivo to down-regulate immunological responses and aid the induction of graft tolerance." @default.
• W2012143342 created "2016-06-24" @default.
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• W2012143342 date "2001-12-01" @default.
• W2012143342 modified "2023-10-12" @default.
• W2012143342 title "DONOR-DERIVED SOLUBLE MHC ANTIGENS PLUS LOW-DOSE CYCLOSPORINE INDUCE TRANSPLANTATION UNRESPONSIVENESS INDEPENDENT OF THE THYMUS BY DOWN-REGULATING T CELL-MEDIATED ALLORESPONSES IN A RAT TRANSPLANTATION MODEL1" @default.
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• W2012143342 doi "https://doi.org/10.1097/00007890-200112270-00018" @default.
• W2012143342 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/11773898" @default.
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