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10.4049/jimmunol.1402034 http://scihub22266oqcxt.onion/10.4049/jimmunol.1402034 C4355388!4355388 !25687759     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=25687759 &cmd=llinks): Failed to open stream: HTTP request failed! 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Transient blockade of delta-like Notch ligands prevents allograft rejection mediated by cellular and humoral mechanisms in a mouse model of heart transplantation |pdf=|usr=}}{{25687759 }} gab.com Text Transient blockade of delta-like Notch ligands prevents allograft rejection mediated by cellular and humoral mechanisms in a mouse model of heart transplantation JO: J Immunol http://www.kidney.de/pget.php?&tw=1&pmid=25687759 #FOAvip Rejection remains a major clinical challenge limiting allograft survival after solid organ transplantation. Both cellular and humoral immunity contribute to this complication, with increased recognition of Ab-mediated damage during acute and chronic rejection. Using a mouse model of MHC-mismatched heart transplantation, we report markedly protective effects of Notch inhibition, dampening both T cell and Ab-driven rejection. T cell-specific pan-Notch blockade prolonged heart allograft survival and decreased IFN-? and IL-4 production by alloreactive T cells, especially when combined with depletion of recipient CD8(+) T cells. These effects were associated with decreased infiltration by conventional T cells and an increased proportion of regulatory T cells in the graft. Transient administration of neutralizing Abs specific for delta-like (Dll)1/4 Notch ligands in the peritransplant period led to prolonged acceptance of allogeneic hearts, with superior outcome over Notch inhibition only in T cells. Systemic Dll1/4 inhibition decreased T cell cytokines and graft infiltration, germinal center B cell and plasmablast numbers, as well as production of donor-specific alloantibodies and complement deposition in the transplanted hearts. Dll1 or Dll4 inhibition alone provided partial protection. Thus, pathogenic signals delivered by Dll1/4 Notch ligands early after transplantation promote organ rejection through several complementary mechanisms. Transient interruption of these signals represents an attractive new therapeutic strategy to enhance long-term allograft survival. Twit Text FOAVip Transient blockade of delta-like Notch ligands prevents allograft rejection mediated by cellular and humoral mechanisms in a mouse model of heart transplantation ????J Immunol http://www.kidney.de/pget.php?&tw=1&pmid=25687759 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=25687759 #FOAvip English Wikipedia <ref>{{Cite pmid|25687759 }}</ref> Transient blockade of delta-like Notch ligands prevents allograft rejection mediated by cellular and humoral mechanisms in a mouse model of heart transplantation #MMPMID25687759 Wood S ; Feng J ; Chung J ; Radojcic V ; Sandy-Sloat AR ; Friedman A ; Shelton A ; Yan M ; Siebel CW ; Bishop DK ; Maillard I J Immunol 2015[Mar]; 194 (6 ): 2899-908 PMID25687759 show ga Rejection remains a major clinical challenge limiting allograft survival after solid organ transplantation. Both cellular and humoral immunity contribute to this complication, with increased recognition of Ab-mediated damage during acute and chronic rejection. Using a mouse model of MHC-mismatched heart transplantation, we report markedly protective effects of Notch inhibition, dampening both T cell and Ab-driven rejection. T cell-specific pan-Notch blockade prolonged heart allograft survival and decreased IFN-? and IL-4 production by alloreactive T cells, especially when combined with depletion of recipient CD8(+) T cells. These effects were associated with decreased infiltration by conventional T cells and an increased proportion of regulatory T cells in the graft. Transient administration of neutralizing Abs specific for delta-like (Dll)1/4 Notch ligands in the peritransplant period led to prolonged acceptance of allogeneic hearts, with superior outcome over Notch inhibition only in T cells. Systemic Dll1/4 inhibition decreased T cell cytokines and graft infiltration, germinal center B cell and plasmablast numbers, as well as production of donor-specific alloantibodies and complement deposition in the transplanted hearts. Dll1 or Dll4 inhibition alone provided partial protection. Thus, pathogenic signals delivered by Dll1/4 Notch ligands early after transplantation promote organ rejection through several complementary mechanisms. Transient interruption of these signals represents an attractive new therapeutic strategy to enhance long-term allograft survival. |Adaptor Proteins, Signal Transducing [MESH] |Animals [MESH] |Antibodies, Neutralizing/*immunology/pharmacology [MESH] |CD8-Positive T-Lymphocytes/drug effects/immunology/metabolism [MESH] |Calcium-Binding Proteins [MESH] |Flow Cytometry [MESH] |Graft Rejection/*immunology/prevention & control [MESH] |Graft Survival/immunology [MESH] |Heart Transplantation/*methods [MESH] |Immunity, Cellular/immunology [MESH] |Immunity, Humoral/immunology [MESH] |Immunity/*immunology [MESH] |Intercellular Signaling Peptides and Proteins/*immunology/metabolism [MESH] |Interferon-gamma/immunology/metabolism [MESH] |Interleukin-4/immunology/metabolism [MESH] |Intracellular Signaling Peptides and Proteins/*immunology/metabolism [MESH] |Membrane Proteins/*immunology/metabolism [MESH] |Mice, Inbred BALB C [MESH] |Mice, Inbred C57BL [MESH] |Mice, Transgenic [MESH] |Receptors, Notch/antagonists & inhibitors/immunology/metabolism [MESH] |Signal Transduction/drug effects/immunology [MESH] |T-Lymphocytes/drug effects/immunology/metabolism [MESH] |Time Factors [MESH]Transient blockade of delta-like Notch ligands prevents allograft reje(epmc).pdf DeepDyve Pubget Overpricing