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10.1172/JCI70522 http://scihub22266oqcxt.onion/10.1172/JCI70522 C4038564!4038564!24762437     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Clin+Invest 2014 ; 124 (6): 2441-55 Nephropedia Template TP {{tp|p=24762437|t=2014. Intrinsic TGF-? signaling promotes age-dependent CD8+ T cell polyfunctionality attrition |pdf=|usr=}}{{24762437}} gab.com Text Intrinsic TGF- signaling promotes age-dependent CD8+ T cell polyfunctionality attrition JO: J Clin Invest http://www.kidney.de/pget.php?&tw=1&pmid=24762437 #FOAvip Advanced age is associated with immune system deficits that result in an increased susceptibility to infectious diseases; however, specific mediators of age-dependent immune dysfunction have not been fully elucidated. Here we demonstrated that aged mice exhibit poor effector CD8+ T cell polyfunctionality, primarily due to CD8+ T cell?extrinsic deficits, and that reduced CD8+ T cell polyfunctionality correlates with increased susceptibility to pathogenic diseases. In aged animals challenged with the parasite Encephalitozoon cuniculi, effector CD8+ T cell survival and polyfunctionality were suppressed by highly elevated TGF-?1. Furthermore, TGF-? depletion reduced effector CD8+ T cell apoptosis in both young and aged mice and enhanced effector CD8+ T cell polyfunctionality in aged mice. Surprisingly, intrinsic blockade of TGF-? signaling in CD8+ T cells was sufficient to rescue polyfunctionality in aged animals. Together, these data demonstrate that low levels of TGF-?1 promote apoptosis of CD8+ effector T cells and high TGF-?1 levels associated with age result in both CD8+ T cell apoptosis and an altered transcriptional profile, which correlates with loss of polyfunctionality. Furthermore, elevated TGF-? levels are observed in the elderly human population and in aged Drosophila, suggesting that TGF-? represents an evolutionarily conserved negative regulator of the immune response in aging organisms. Twit Text FOAVip Intrinsic TGF- signaling promotes age-dependent CD8+ T cell polyfunctionality attrition ????J Clin Invest http://www.kidney.de/pget.php?&tw=1&pmid=24762437 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=24762437 #FOAvip English Wikipedia <ref>{{Cite pmid|24762437}}</ref> Intrinsic TGF-? signaling promotes age-dependent CD8+ T cell polyfunctionality attrition #MMPMID24762437 Bhadra R; Moretto MM; Castillo JC; Petrovas C; Ferrando-Martinez S; Shokal U; Leal M; Koup RA; Eleftherianos I; Khan IA J Clin Invest 2014[Jun]; 124 (6): 2441-55 PMID24762437show ga Advanced age is associated with immune system deficits that result in an increased susceptibility to infectious diseases; however, specific mediators of age-dependent immune dysfunction have not been fully elucidated. Here we demonstrated that aged mice exhibit poor effector CD8+ T cell polyfunctionality, primarily due to CD8+ T cell?extrinsic deficits, and that reduced CD8+ T cell polyfunctionality correlates with increased susceptibility to pathogenic diseases. In aged animals challenged with the parasite Encephalitozoon cuniculi, effector CD8+ T cell survival and polyfunctionality were suppressed by highly elevated TGF-?1. Furthermore, TGF-? depletion reduced effector CD8+ T cell apoptosis in both young and aged mice and enhanced effector CD8+ T cell polyfunctionality in aged mice. Surprisingly, intrinsic blockade of TGF-? signaling in CD8+ T cells was sufficient to rescue polyfunctionality in aged animals. Together, these data demonstrate that low levels of TGF-?1 promote apoptosis of CD8+ effector T cells and high TGF-?1 levels associated with age result in both CD8+ T cell apoptosis and an altered transcriptional profile, which correlates with loss of polyfunctionality. Furthermore, elevated TGF-? levels are observed in the elderly human population and in aged Drosophila, suggesting that TGF-? represents an evolutionarily conserved negative regulator of the immune response in aging organisms. äIntrinsic TGF-? signaling promotes age-dependent CD8+ T cell polyfunct(epmc).pdf DeepDyve Pubget Overpricing