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10.1172/jci.insight.92033 http://scihub22266oqcxt.onion/10.1172/jci.insight.92033 C5414557!5414557!28469082     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=28469082&cmd=llinks): Failed to open stream: HTTP request failed! 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CTLA4-Ig in combination with FTY720 promotes allograft survival in sensitized recipients |pdf=|usr=}}{{28469082}} gab.com Text CTLA4-Ig in combination with FTY720 promotes allograft survival in sensitized recipients JO: JCI Insight http://www.kidney.de/pget.php?&tw=1&pmid=28469082 #FOAvip Despite recent evidence of improved graft outcomes and safety, the high incidence of early acute cellular rejection with belatacept, a high-affinity CTLA4-Ig, has limited its use in clinical transplantation. Here we define how the incomplete control of endogenous donor-reactive memory T cells results in belatacept-resistant rejection in an experimental model of BALB/c.2W-OVA donor heart transplantation into C57BL/6 recipients presensitized to donor splenocytes. These sensitized mice harbored modestly elevated numbers of endogenous donor-specific memory T cells and alloantibodies compared with naive recipients. Continuous CTLA4-Ig treatment was unexpectedly efficacious at inhibiting endogenous graft-reactive T cell expansion but was unable to inhibit late CD4+ and CD8+ T cell infiltration into the allografts, and rejection was observed in 50% of recipients by day 35 after transplantation. When CTLA4-Ig was combined with the sphingosine 1-phosphate receptor-1 (S1PR1) functional antagonist FTY720, alloantibody production was inhibited and donor-specific IFN-??producing T cells were reduced to levels approaching nonsensitized tolerant recipients. Late T cell recruitment into the graft was also restrained, and graft survival improved with this combination therapy. These observations suggest that a rational strategy consisting of inhibiting memory T cell expansion and trafficking into the allograft with CTLA4-Ig and FTY720 can promote allograft survival in allosensitized recipients. Twit Text FOAVip CTLA4-Ig in combination with FTY720 promotes allograft survival in sensitized recipients ????JCI Insight http://www.kidney.de/pget.php?&tw=1&pmid=28469082 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=28469082 #FOAvip English Wikipedia <ref>{{Cite pmid|28469082}}</ref> CTLA4-Ig in combination with FTY720 promotes allograft survival in sensitized recipients #MMPMID28469082 Khiew SH; Yang J; Young JS; Chen J; Wang Q; Yin D; Vu V; Miller ML; Sciammas R; Alegre ML; Chong AS JCI Insight ä[]; 2 (9): ä PMID28469082show ga Despite recent evidence of improved graft outcomes and safety, the high incidence of early acute cellular rejection with belatacept, a high-affinity CTLA4-Ig, has limited its use in clinical transplantation. Here we define how the incomplete control of endogenous donor-reactive memory T cells results in belatacept-resistant rejection in an experimental model of BALB/c.2W-OVA donor heart transplantation into C57BL/6 recipients presensitized to donor splenocytes. These sensitized mice harbored modestly elevated numbers of endogenous donor-specific memory T cells and alloantibodies compared with naive recipients. Continuous CTLA4-Ig treatment was unexpectedly efficacious at inhibiting endogenous graft-reactive T cell expansion but was unable to inhibit late CD4+ and CD8+ T cell infiltration into the allografts, and rejection was observed in 50% of recipients by day 35 after transplantation. When CTLA4-Ig was combined with the sphingosine 1-phosphate receptor-1 (S1PR1) functional antagonist FTY720, alloantibody production was inhibited and donor-specific IFN-??producing T cells were reduced to levels approaching nonsensitized tolerant recipients. Late T cell recruitment into the graft was also restrained, and graft survival improved with this combination therapy. These observations suggest that a rational strategy consisting of inhibiting memory T cell expansion and trafficking into the allograft with CTLA4-Ig and FTY720 can promote allograft survival in allosensitized recipients. äCTLA4-Ig in combination with FTY720 promotes allograft survival in sen(epmc).pdf DeepDyve Pubget Overpricing