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10.3389/fimmu.2018.00446 http://scihub22266oqcxt.onion/10.3389/fimmu.2018.00446 C5845988!5845988 !29563914     free     free     free Deprecated: Implicit conversion from float 223.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 223.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 223.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 223.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 223.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 223.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 223.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 257.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 257.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\29563914 .jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Front+Immunol 2018 ; 9 (ä): 446 Nephropedia Template TP {{tp|p=29563914 |t=2018. Exhaustion of the CD8(+) T Cell Compartment in Patients with Mutations in Phosphoinositide 3-Kinase Delta |pdf=|usr=}}{{29563914 }} gab.com Text Exhaustion of the CD8(+) T Cell Compartment in Patients with Mutations in Phosphoinositide 3-Kinase Delta JO: Front Immunol http://www.kidney.de/pget.php?&tw=1&pmid=29563914 #FOAvip Pathogenic gain-of-function mutations in the gene encoding phosphoinositide 3-kinase delta (PI3K?) cause activated PI3K? syndrome (APDS), a disease characterized by humoral immunodeficiency, lymphadenopathy, and an inability to control persistent viral infections including Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections. Understanding the mechanisms leading to impaired immune response is important to optimally treat APDS patients. Immunosenescence of CD8(+) T cells was suggested to contribute to APDS pathogenesis. However, the constitutive activation of T cells in APDS may also result in T cell exhaustion. Therefore, we studied exhaustion of the CD8(+) T cell compartment in APDS patients and compared them with healthy controls and HIV patients, as a control for exhaustion. The subset distribution of the T cell compartment of APDS patients was comparable with HIV patients with decreased naive CD4(+) and CD8(+) T cells and increased effector CD8(+) T cells. Like in HIV(+) patients, expression of activation markers and inhibitory receptors CD160, CD244, and programmed death receptor (PD)-1 on CD8(+) T cells was increased in APDS patients, indicating exhaustion. EBV-specific CD8(+) T cells from APDS patients exhibited an exhausted phenotype that resembled HIV-specific CD8(+) T cells in terms of inhibitory receptor expression. Inhibition of PD-1 on EBV-specific CD8(+) T cells from APDS patients enhanced in vitro proliferation and effector cytokine production. Based on these results, we conclude that total and EBV-specific CD8(+) T cells from APDS patients are characterized by T cell exhaustion. Furthermore, PD-1 checkpoint inhibition may provide a possible therapeutic approach to support the immune system of APDS patients to control EBV and CMV. Twit Text FOAVip Exhaustion of the CD8(+) T Cell Compartment in Patients with Mutations in Phosphoinositide 3-Kinase Delta ????Front Immunol http://www.kidney.de/pget.php?&tw=1&pmid=29563914 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=29563914 #FOAvip English Wikipedia <ref>{{Cite pmid|29563914 }}</ref> Exhaustion of the CD8(+) T Cell Compartment in Patients with Mutations in Phosphoinositide 3-Kinase Delta #MMPMID29563914 Wentink MWJ ; Mueller YM ; Dalm VASH ; Driessen GJ ; van Hagen PM ; van Montfrans JM ; van der Burg M ; Katsikis PD Front Immunol 2018[]; 9 (ä): 446 PMID29563914 show ga Pathogenic gain-of-function mutations in the gene encoding phosphoinositide 3-kinase delta (PI3K?) cause activated PI3K? syndrome (APDS), a disease characterized by humoral immunodeficiency, lymphadenopathy, and an inability to control persistent viral infections including Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infections. Understanding the mechanisms leading to impaired immune response is important to optimally treat APDS patients. Immunosenescence of CD8(+) T cells was suggested to contribute to APDS pathogenesis. However, the constitutive activation of T cells in APDS may also result in T cell exhaustion. Therefore, we studied exhaustion of the CD8(+) T cell compartment in APDS patients and compared them with healthy controls and HIV patients, as a control for exhaustion. The subset distribution of the T cell compartment of APDS patients was comparable with HIV patients with decreased naive CD4(+) and CD8(+) T cells and increased effector CD8(+) T cells. Like in HIV(+) patients, expression of activation markers and inhibitory receptors CD160, CD244, and programmed death receptor (PD)-1 on CD8(+) T cells was increased in APDS patients, indicating exhaustion. EBV-specific CD8(+) T cells from APDS patients exhibited an exhausted phenotype that resembled HIV-specific CD8(+) T cells in terms of inhibitory receptor expression. Inhibition of PD-1 on EBV-specific CD8(+) T cells from APDS patients enhanced in vitro proliferation and effector cytokine production. Based on these results, we conclude that total and EBV-specific CD8(+) T cells from APDS patients are characterized by T cell exhaustion. Furthermore, PD-1 checkpoint inhibition may provide a possible therapeutic approach to support the immune system of APDS patients to control EBV and CMV. |Adolescent [MESH] |Adult [MESH] |CD8-Positive T-Lymphocytes/*immunology [MESH] |Cell Proliferation [MESH] |Cells, Cultured [MESH] |Cellular Senescence [MESH] |Child [MESH] |Class I Phosphatidylinositol 3-Kinases/*genetics/immunology [MESH] |Cytokines/metabolism [MESH] |Female [MESH] |Humans [MESH] |Immunologic Deficiency Syndromes/genetics/*immunology [MESH] |Immunophenotyping [MESH] |Lymphocyte Activation [MESH] |Male [MESH] |Mutation/*genetics [MESH] |Primary Immunodeficiency Diseases [MESH] |Programmed Cell Death 1 Receptor/metabolism [MESH] |T-Lymphocyte Subsets/*immunology [MESH] |Virus Diseases/genetics/*immunology [MESH]Exhaustion of the CD8(+) T Cell Compartment in Patients with Mutations(epmc).pdf DeepDyve Pubget Overpricing