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10.1038/nature19330 http://scihub22266oqcxt.onion/10.1038/nature19330 C5297183!5297183!27501248     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Nature 2016 ; 537 (7620): 417-21 Nephropedia Template TP {{tp|p=27501248|t=2016. Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy |pdf=|usr=}}{{27501248}} gab.com Text Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy JO: Nature http://www.kidney.de/pget.php?&tw=1&pmid=27501248 #FOAvip Chronic viral infections are characterized by a state of CD8+ T-cell dysfunction that is associated with expression of the programmed cell death 1 (PD-1) inhibitory receptor1?4. A better understanding of the mechanisms that regulate CD8+ T cell responses during chronic infection is required to improve immunotherapies that restore function in exhausted CD8+ T cells. Here we identify a population of virus-specific CD8+ T cells that proliferate after blockade of the PD-1 inhibitory pathway in mice chronically infected with lymphocytic choriomeningitis virus (LCMV). These LCMV-specific CD8+ T cells expressed the PD-1 inhibitory receptor but also expressed several costimulatory molecules such as ICOS and CD28. This CD8+ T cell subset was characterized by a unique gene signature that was related to that of CD4+ T follicular helper (TFH) cells, CD8+ T cell memory precursors and haematopoietic stem cell progenitors, but that was distinct from that of CD4+ TH1 cells and CD8+ terminal effectors. This CD8+ T cell population was found only in lymphoid tissues and resided predominantly in the T cell zones along with naïve CD8+ T cells. These PD-1+ CD8+ T cells resembled stem cells during chronic LCMV infection, undergoing self-renewal and also differentiating into the terminally exhausted CD8+ T cells that were present in both lymphoid and non-lymphoid tissues. The proliferative burst after PD-1 blockade came almost exclusively from this CD8+ T cell subset. Notably, the transcription factor TCF1 had a cell intrinsic and essential role in the generation of this CD8+ T cell subset. These findings provide a better understanding of T cell exhaustion and have implications in the optimization of PD-1-directed immunotherapy in chronic infections and cancer. Twit Text FOAVip Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy ????Nature http://www.kidney.de/pget.php?&tw=1&pmid=27501248 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=27501248 #FOAvip English Wikipedia <ref>{{Cite pmid|27501248}}</ref> Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy #MMPMID27501248 Im SJ; Hashimoto M; Gerner MY; Lee J; Kissick HT; Burger MC; Shan Q; Hale JS; Lee J; Nasti TH; Sharpe AH; Freeman GJ; Germain RN; Nakaya HI; Xue HH; Ahmed R Nature 2016[Sep]; 537 (7620): 417-21 PMID27501248show ga Chronic viral infections are characterized by a state of CD8+ T-cell dysfunction that is associated with expression of the programmed cell death 1 (PD-1) inhibitory receptor1?4. A better understanding of the mechanisms that regulate CD8+ T cell responses during chronic infection is required to improve immunotherapies that restore function in exhausted CD8+ T cells. Here we identify a population of virus-specific CD8+ T cells that proliferate after blockade of the PD-1 inhibitory pathway in mice chronically infected with lymphocytic choriomeningitis virus (LCMV). These LCMV-specific CD8+ T cells expressed the PD-1 inhibitory receptor but also expressed several costimulatory molecules such as ICOS and CD28. This CD8+ T cell subset was characterized by a unique gene signature that was related to that of CD4+ T follicular helper (TFH) cells, CD8+ T cell memory precursors and haematopoietic stem cell progenitors, but that was distinct from that of CD4+ TH1 cells and CD8+ terminal effectors. This CD8+ T cell population was found only in lymphoid tissues and resided predominantly in the T cell zones along with naïve CD8+ T cells. These PD-1+ CD8+ T cells resembled stem cells during chronic LCMV infection, undergoing self-renewal and also differentiating into the terminally exhausted CD8+ T cells that were present in both lymphoid and non-lymphoid tissues. The proliferative burst after PD-1 blockade came almost exclusively from this CD8+ T cell subset. Notably, the transcription factor TCF1 had a cell intrinsic and essential role in the generation of this CD8+ T cell subset. These findings provide a better understanding of T cell exhaustion and have implications in the optimization of PD-1-directed immunotherapy in chronic infections and cancer. äDefining CD8+ T cells that provide the proliferative burst after PD-1 (epmc).pdf DeepDyve Pubget Overpricing