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10.18632/oncotarget.15551

http://scihub22266oqcxt.onion/10.18632/oncotarget.15551
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suck abstract from ncbi


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pmid28445940
      Oncotarget 2017 ; 8 (15 ): 24187-24195
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  • Suppression of allograft rejection by CD8+CD122+PD-1+ Tregs is dictated by their Fas ligand-initiated killing of effector T cells versus Fas-mediated own apoptosis #MMPMID28445940
  • Liu H ; Wang Y ; Zeng Q ; Zeng YQ ; Liang CL ; Qiu F ; Nie H ; Dai Z
  • Oncotarget 2017[Apr]; 8 (15 ): 24187-24195 PMID28445940 show ga
  • Mounting evidence has shown that naturally occurring CD8+CD122+ T cells are regulatory T cells (Tregs) that suppress both autoimmunity and alloimmunity. We have previously shown that CD8+CD122+PD-1+ Tregs not only suppress allograft rejection, but also are more potent in suppression than conventional CD4+CD25+ Tregs. However, the mechanisms underlying their suppression of alloimmunity are not well understood. In an adoptive T-cell transfer model of mice lacking lymphocytes, we found that suppression of skin allograft rejection by CD8+CD122+PD-1+ Tregs was mostly dependent on their expression of Fas ligand as either lacking Fas ligand or blocking it with antibodies largely abolished their suppression of allograft rejection mediated by transferred T cells. Their suppression was also mostly reversed when effector T cells lacked Fas receptor. Indeed, these FasL+ Tregs induced T cell apoptosis in vitro in a Fas/FasL-dependent manner. However, their suppression of T cell proliferation in vitro was dependent on IL-10, but not FasL expression. Furthermore, adoptive transfer of CD8+CD122+PD-1+ Tregs significantly extended allograft survival even in wild-type mice if Tregs lacked Fas receptor or if recipients received recombinant IL-15, as these two measures synergistically expanded adoptively-transferred Tregs in recipients. Thus, this study may have important implications for Treg therapies in clinical transplantation.
  • |*Apoptosis/immunology [MESH]
  • |Allografts [MESH]
  • |Animals [MESH]
  • |Biomarkers [MESH]
  • |CD8-Positive T-Lymphocytes/immunology/metabolism [MESH]
  • |Cytotoxicity, Immunologic [MESH]
  • |Fas Ligand Protein/*metabolism [MESH]
  • |Graft Rejection/*immunology [MESH]
  • |Immunomodulation [MESH]
  • |Interleukin-2 Receptor beta Subunit/metabolism [MESH]
  • |Lymphocyte Activation/genetics/immunology [MESH]
  • |Mice [MESH]
  • |Mice, Knockout [MESH]
  • |Phenotype [MESH]
  • |Programmed Cell Death 1 Receptor/metabolism [MESH]
  • |Signal Transduction [MESH]
  • |T-Lymphocyte Subsets/*immunology/*metabolism [MESH]
  • |T-Lymphocytes, Regulatory/*immunology/*metabolism [MESH]


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