TIGIT Marks Exhausted T Cells, Correlates with Disease Progression, and Serves as a Target for Immune Restoration in HIV and SIV Infection.

HIV infection induces phenotypic and functional changes to CD8+ T cells defined by the coordinated upregulation of a series of negative checkpoint receptors that eventually result in T cell exhaustion and failure to control viral replication. We report that effector CD8+ T cells during HIV infection...
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Autor*in:	Glen M Chew [verfasserIn] Tsuyoshi Fujita [verfasserIn] Gabriela M Webb [verfasserIn] Benjamin J Burwitz [verfasserIn] Helen L Wu [verfasserIn] Jason S Reed [verfasserIn] Katherine B Hammond [verfasserIn] Kiera L Clayton [verfasserIn] Naoto Ishii [verfasserIn] Mohamed Abdel-Mohsen [verfasserIn] Teri Liegler [verfasserIn] Brooks I Mitchell [verfasserIn] Frederick M Hecht [verfasserIn] Mario Ostrowski [verfasserIn] Cecilia M Shikuma [verfasserIn] Scott G Hansen [verfasserIn] Mark Maurer [verfasserIn] Alan J Korman [verfasserIn] Steven G Deeks [verfasserIn] Jonah B Sacha [verfasserIn] Lishomwa C Ndhlovu [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2016

Übergeordnetes Werk:	In: PLoS Pathogens - Public Library of Science (PLoS), 2005, 12(2016), 1, p e1005349
Übergeordnetes Werk:	volume:12 ; year:2016 ; number:1, p e1005349

Links:	Link aufrufen Link aufrufen Link aufrufen Journal toc Journal toc

DOI / URN:	10.1371/journal.ppat.1005349

Katalog-ID:	DOAJ077367561

Internformat


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520			\|a HIV infection induces phenotypic and functional changes to CD8+ T cells defined by the coordinated upregulation of a series of negative checkpoint receptors that eventually result in T cell exhaustion and failure to control viral replication. We report that effector CD8+ T cells during HIV infection in blood and SIV infection in lymphoid tissue exhibit higher levels of the negative checkpoint receptor TIGIT. Increased frequencies of TIGIT+ and TIGIT+ PD-1+ CD8+ T cells correlated with parameters of HIV and SIV disease progression. TIGIT remained elevated despite viral suppression in those with either pharmacological antiretroviral control or immunologically in elite controllers. HIV and SIV-specific CD8+ T cells were dysfunctional and expressed high levels of TIGIT and PD-1. Ex-vivo single or combinational antibody blockade of TIGIT and/or PD-L1 restored viral-specific CD8+ T cell effector responses. The frequency of TIGIT+ CD4+ T cells correlated with the CD4+ T cell total HIV DNA. These findings identify TIGIT as a novel marker of dysfunctional HIV-specific T cells and suggest TIGIT along with other checkpoint receptors may be novel curative HIV targets to reverse T cell exhaustion.
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allfields	10.1371/journal.ppat.1005349 doi (DE-627)DOAJ077367561 (DE-599)DOAJ98d1b0911eb74042a13b8e84449dee0c DE-627 ger DE-627 rakwb eng RC581-607 QH301-705.5 Glen M Chew verfasserin aut TIGIT Marks Exhausted T Cells, Correlates with Disease Progression, and Serves as a Target for Immune Restoration in HIV and SIV Infection. 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier HIV infection induces phenotypic and functional changes to CD8+ T cells defined by the coordinated upregulation of a series of negative checkpoint receptors that eventually result in T cell exhaustion and failure to control viral replication. We report that effector CD8+ T cells during HIV infection in blood and SIV infection in lymphoid tissue exhibit higher levels of the negative checkpoint receptor TIGIT. Increased frequencies of TIGIT+ and TIGIT+ PD-1+ CD8+ T cells correlated with parameters of HIV and SIV disease progression. TIGIT remained elevated despite viral suppression in those with either pharmacological antiretroviral control or immunologically in elite controllers. HIV and SIV-specific CD8+ T cells were dysfunctional and expressed high levels of TIGIT and PD-1. Ex-vivo single or combinational antibody blockade of TIGIT and/or PD-L1 restored viral-specific CD8+ T cell effector responses. The frequency of TIGIT+ CD4+ T cells correlated with the CD4+ T cell total HIV DNA. These findings identify TIGIT as a novel marker of dysfunctional HIV-specific T cells and suggest TIGIT along with other checkpoint receptors may be novel curative HIV targets to reverse T cell exhaustion. Immunologic diseases. Allergy Biology (General) Tsuyoshi Fujita verfasserin aut Gabriela M Webb verfasserin aut Benjamin J Burwitz verfasserin aut Helen L Wu verfasserin aut Jason S Reed verfasserin aut Katherine B Hammond verfasserin aut Kiera L Clayton verfasserin aut Naoto Ishii verfasserin aut Mohamed Abdel-Mohsen verfasserin aut Teri Liegler verfasserin aut Brooks I Mitchell verfasserin aut Frederick M Hecht verfasserin aut Mario Ostrowski verfasserin aut Cecilia M Shikuma verfasserin aut Scott G Hansen verfasserin aut Mark Maurer verfasserin aut Alan J Korman verfasserin aut Steven G Deeks verfasserin aut Jonah B Sacha verfasserin aut Lishomwa C Ndhlovu verfasserin aut In PLoS Pathogens Public Library of Science (PLoS), 2005 12(2016), 1, p e1005349 (DE-627)501074422 (DE-600)2205412-1 15537374 nnns volume:12 year:2016 number:1, p e1005349 https://doi.org/10.1371/journal.ppat.1005349 kostenfrei https://doaj.org/article/98d1b0911eb74042a13b8e84449dee0c kostenfrei https://doi.org/10.1371/journal.ppat.1005349 kostenfrei https://doaj.org/toc/1553-7366 Journal toc kostenfrei https://doaj.org/toc/1553-7374 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2016 1, p e1005349
spelling	10.1371/journal.ppat.1005349 doi (DE-627)DOAJ077367561 (DE-599)DOAJ98d1b0911eb74042a13b8e84449dee0c DE-627 ger DE-627 rakwb eng RC581-607 QH301-705.5 Glen M Chew verfasserin aut TIGIT Marks Exhausted T Cells, Correlates with Disease Progression, and Serves as a Target for Immune Restoration in HIV and SIV Infection. 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier HIV infection induces phenotypic and functional changes to CD8+ T cells defined by the coordinated upregulation of a series of negative checkpoint receptors that eventually result in T cell exhaustion and failure to control viral replication. We report that effector CD8+ T cells during HIV infection in blood and SIV infection in lymphoid tissue exhibit higher levels of the negative checkpoint receptor TIGIT. Increased frequencies of TIGIT+ and TIGIT+ PD-1+ CD8+ T cells correlated with parameters of HIV and SIV disease progression. TIGIT remained elevated despite viral suppression in those with either pharmacological antiretroviral control or immunologically in elite controllers. HIV and SIV-specific CD8+ T cells were dysfunctional and expressed high levels of TIGIT and PD-1. Ex-vivo single or combinational antibody blockade of TIGIT and/or PD-L1 restored viral-specific CD8+ T cell effector responses. The frequency of TIGIT+ CD4+ T cells correlated with the CD4+ T cell total HIV DNA. These findings identify TIGIT as a novel marker of dysfunctional HIV-specific T cells and suggest TIGIT along with other checkpoint receptors may be novel curative HIV targets to reverse T cell exhaustion. Immunologic diseases. Allergy Biology (General) Tsuyoshi Fujita verfasserin aut Gabriela M Webb verfasserin aut Benjamin J Burwitz verfasserin aut Helen L Wu verfasserin aut Jason S Reed verfasserin aut Katherine B Hammond verfasserin aut Kiera L Clayton verfasserin aut Naoto Ishii verfasserin aut Mohamed Abdel-Mohsen verfasserin aut Teri Liegler verfasserin aut Brooks I Mitchell verfasserin aut Frederick M Hecht verfasserin aut Mario Ostrowski verfasserin aut Cecilia M Shikuma verfasserin aut Scott G Hansen verfasserin aut Mark Maurer verfasserin aut Alan J Korman verfasserin aut Steven G Deeks verfasserin aut Jonah B Sacha verfasserin aut Lishomwa C Ndhlovu verfasserin aut In PLoS Pathogens Public Library of Science (PLoS), 2005 12(2016), 1, p e1005349 (DE-627)501074422 (DE-600)2205412-1 15537374 nnns volume:12 year:2016 number:1, p e1005349 https://doi.org/10.1371/journal.ppat.1005349 kostenfrei https://doaj.org/article/98d1b0911eb74042a13b8e84449dee0c kostenfrei https://doi.org/10.1371/journal.ppat.1005349 kostenfrei https://doaj.org/toc/1553-7366 Journal toc kostenfrei https://doaj.org/toc/1553-7374 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2016 1, p e1005349
allfields_unstemmed	10.1371/journal.ppat.1005349 doi (DE-627)DOAJ077367561 (DE-599)DOAJ98d1b0911eb74042a13b8e84449dee0c DE-627 ger DE-627 rakwb eng RC581-607 QH301-705.5 Glen M Chew verfasserin aut TIGIT Marks Exhausted T Cells, Correlates with Disease Progression, and Serves as a Target for Immune Restoration in HIV and SIV Infection. 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier HIV infection induces phenotypic and functional changes to CD8+ T cells defined by the coordinated upregulation of a series of negative checkpoint receptors that eventually result in T cell exhaustion and failure to control viral replication. We report that effector CD8+ T cells during HIV infection in blood and SIV infection in lymphoid tissue exhibit higher levels of the negative checkpoint receptor TIGIT. Increased frequencies of TIGIT+ and TIGIT+ PD-1+ CD8+ T cells correlated with parameters of HIV and SIV disease progression. TIGIT remained elevated despite viral suppression in those with either pharmacological antiretroviral control or immunologically in elite controllers. HIV and SIV-specific CD8+ T cells were dysfunctional and expressed high levels of TIGIT and PD-1. Ex-vivo single or combinational antibody blockade of TIGIT and/or PD-L1 restored viral-specific CD8+ T cell effector responses. The frequency of TIGIT+ CD4+ T cells correlated with the CD4+ T cell total HIV DNA. These findings identify TIGIT as a novel marker of dysfunctional HIV-specific T cells and suggest TIGIT along with other checkpoint receptors may be novel curative HIV targets to reverse T cell exhaustion. Immunologic diseases. Allergy Biology (General) Tsuyoshi Fujita verfasserin aut Gabriela M Webb verfasserin aut Benjamin J Burwitz verfasserin aut Helen L Wu verfasserin aut Jason S Reed verfasserin aut Katherine B Hammond verfasserin aut Kiera L Clayton verfasserin aut Naoto Ishii verfasserin aut Mohamed Abdel-Mohsen verfasserin aut Teri Liegler verfasserin aut Brooks I Mitchell verfasserin aut Frederick M Hecht verfasserin aut Mario Ostrowski verfasserin aut Cecilia M Shikuma verfasserin aut Scott G Hansen verfasserin aut Mark Maurer verfasserin aut Alan J Korman verfasserin aut Steven G Deeks verfasserin aut Jonah B Sacha verfasserin aut Lishomwa C Ndhlovu verfasserin aut In PLoS Pathogens Public Library of Science (PLoS), 2005 12(2016), 1, p e1005349 (DE-627)501074422 (DE-600)2205412-1 15537374 nnns volume:12 year:2016 number:1, p e1005349 https://doi.org/10.1371/journal.ppat.1005349 kostenfrei https://doaj.org/article/98d1b0911eb74042a13b8e84449dee0c kostenfrei https://doi.org/10.1371/journal.ppat.1005349 kostenfrei https://doaj.org/toc/1553-7366 Journal toc kostenfrei https://doaj.org/toc/1553-7374 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2016 1, p e1005349
allfieldsGer	10.1371/journal.ppat.1005349 doi (DE-627)DOAJ077367561 (DE-599)DOAJ98d1b0911eb74042a13b8e84449dee0c DE-627 ger DE-627 rakwb eng RC581-607 QH301-705.5 Glen M Chew verfasserin aut TIGIT Marks Exhausted T Cells, Correlates with Disease Progression, and Serves as a Target for Immune Restoration in HIV and SIV Infection. 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier HIV infection induces phenotypic and functional changes to CD8+ T cells defined by the coordinated upregulation of a series of negative checkpoint receptors that eventually result in T cell exhaustion and failure to control viral replication. We report that effector CD8+ T cells during HIV infection in blood and SIV infection in lymphoid tissue exhibit higher levels of the negative checkpoint receptor TIGIT. Increased frequencies of TIGIT+ and TIGIT+ PD-1+ CD8+ T cells correlated with parameters of HIV and SIV disease progression. TIGIT remained elevated despite viral suppression in those with either pharmacological antiretroviral control or immunologically in elite controllers. HIV and SIV-specific CD8+ T cells were dysfunctional and expressed high levels of TIGIT and PD-1. Ex-vivo single or combinational antibody blockade of TIGIT and/or PD-L1 restored viral-specific CD8+ T cell effector responses. The frequency of TIGIT+ CD4+ T cells correlated with the CD4+ T cell total HIV DNA. These findings identify TIGIT as a novel marker of dysfunctional HIV-specific T cells and suggest TIGIT along with other checkpoint receptors may be novel curative HIV targets to reverse T cell exhaustion. Immunologic diseases. Allergy Biology (General) Tsuyoshi Fujita verfasserin aut Gabriela M Webb verfasserin aut Benjamin J Burwitz verfasserin aut Helen L Wu verfasserin aut Jason S Reed verfasserin aut Katherine B Hammond verfasserin aut Kiera L Clayton verfasserin aut Naoto Ishii verfasserin aut Mohamed Abdel-Mohsen verfasserin aut Teri Liegler verfasserin aut Brooks I Mitchell verfasserin aut Frederick M Hecht verfasserin aut Mario Ostrowski verfasserin aut Cecilia M Shikuma verfasserin aut Scott G Hansen verfasserin aut Mark Maurer verfasserin aut Alan J Korman verfasserin aut Steven G Deeks verfasserin aut Jonah B Sacha verfasserin aut Lishomwa C Ndhlovu verfasserin aut In PLoS Pathogens Public Library of Science (PLoS), 2005 12(2016), 1, p e1005349 (DE-627)501074422 (DE-600)2205412-1 15537374 nnns volume:12 year:2016 number:1, p e1005349 https://doi.org/10.1371/journal.ppat.1005349 kostenfrei https://doaj.org/article/98d1b0911eb74042a13b8e84449dee0c kostenfrei https://doi.org/10.1371/journal.ppat.1005349 kostenfrei https://doaj.org/toc/1553-7366 Journal toc kostenfrei https://doaj.org/toc/1553-7374 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2016 1, p e1005349
allfieldsSound	10.1371/journal.ppat.1005349 doi (DE-627)DOAJ077367561 (DE-599)DOAJ98d1b0911eb74042a13b8e84449dee0c DE-627 ger DE-627 rakwb eng RC581-607 QH301-705.5 Glen M Chew verfasserin aut TIGIT Marks Exhausted T Cells, Correlates with Disease Progression, and Serves as a Target for Immune Restoration in HIV and SIV Infection. 2016 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier HIV infection induces phenotypic and functional changes to CD8+ T cells defined by the coordinated upregulation of a series of negative checkpoint receptors that eventually result in T cell exhaustion and failure to control viral replication. We report that effector CD8+ T cells during HIV infection in blood and SIV infection in lymphoid tissue exhibit higher levels of the negative checkpoint receptor TIGIT. Increased frequencies of TIGIT+ and TIGIT+ PD-1+ CD8+ T cells correlated with parameters of HIV and SIV disease progression. TIGIT remained elevated despite viral suppression in those with either pharmacological antiretroviral control or immunologically in elite controllers. HIV and SIV-specific CD8+ T cells were dysfunctional and expressed high levels of TIGIT and PD-1. Ex-vivo single or combinational antibody blockade of TIGIT and/or PD-L1 restored viral-specific CD8+ T cell effector responses. The frequency of TIGIT+ CD4+ T cells correlated with the CD4+ T cell total HIV DNA. These findings identify TIGIT as a novel marker of dysfunctional HIV-specific T cells and suggest TIGIT along with other checkpoint receptors may be novel curative HIV targets to reverse T cell exhaustion. Immunologic diseases. Allergy Biology (General) Tsuyoshi Fujita verfasserin aut Gabriela M Webb verfasserin aut Benjamin J Burwitz verfasserin aut Helen L Wu verfasserin aut Jason S Reed verfasserin aut Katherine B Hammond verfasserin aut Kiera L Clayton verfasserin aut Naoto Ishii verfasserin aut Mohamed Abdel-Mohsen verfasserin aut Teri Liegler verfasserin aut Brooks I Mitchell verfasserin aut Frederick M Hecht verfasserin aut Mario Ostrowski verfasserin aut Cecilia M Shikuma verfasserin aut Scott G Hansen verfasserin aut Mark Maurer verfasserin aut Alan J Korman verfasserin aut Steven G Deeks verfasserin aut Jonah B Sacha verfasserin aut Lishomwa C Ndhlovu verfasserin aut In PLoS Pathogens Public Library of Science (PLoS), 2005 12(2016), 1, p e1005349 (DE-627)501074422 (DE-600)2205412-1 15537374 nnns volume:12 year:2016 number:1, p e1005349 https://doi.org/10.1371/journal.ppat.1005349 kostenfrei https://doaj.org/article/98d1b0911eb74042a13b8e84449dee0c kostenfrei https://doi.org/10.1371/journal.ppat.1005349 kostenfrei https://doaj.org/toc/1553-7366 Journal toc kostenfrei https://doaj.org/toc/1553-7374 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_2522 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 12 2016 1, p e1005349
language	English
source	In PLoS Pathogens 12(2016), 1, p e1005349 volume:12 year:2016 number:1, p e1005349
sourceStr	In PLoS Pathogens 12(2016), 1, p e1005349 volume:12 year:2016 number:1, p e1005349
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Immunologic diseases. Allergy Biology (General)
isfreeaccess_bool	true
container_title	PLoS Pathogens
authorswithroles_txt_mv	Glen M Chew @@aut@@ Tsuyoshi Fujita @@aut@@ Gabriela M Webb @@aut@@ Benjamin J Burwitz @@aut@@ Helen L Wu @@aut@@ Jason S Reed @@aut@@ Katherine B Hammond @@aut@@ Kiera L Clayton @@aut@@ Naoto Ishii @@aut@@ Mohamed Abdel-Mohsen @@aut@@ Teri Liegler @@aut@@ Brooks I Mitchell @@aut@@ Frederick M Hecht @@aut@@ Mario Ostrowski @@aut@@ Cecilia M Shikuma @@aut@@ Scott G Hansen @@aut@@ Mark Maurer @@aut@@ Alan J Korman @@aut@@ Steven G Deeks @@aut@@ Jonah B Sacha @@aut@@ Lishomwa C Ndhlovu @@aut@@
publishDateDaySort_date	2016-01-01T00:00:00Z
hierarchy_top_id	501074422
id	DOAJ077367561
language_de	englisch
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callnumber-first	R - Medicine
author	Glen M Chew
spellingShingle	Glen M Chew misc RC581-607 misc QH301-705.5 misc Immunologic diseases. Allergy misc Biology (General) TIGIT Marks Exhausted T Cells, Correlates with Disease Progression, and Serves as a Target for Immune Restoration in HIV and SIV Infection.
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topic_title	RC581-607 QH301-705.5 TIGIT Marks Exhausted T Cells, Correlates with Disease Progression, and Serves as a Target for Immune Restoration in HIV and SIV Infection
topic	misc RC581-607 misc QH301-705.5 misc Immunologic diseases. Allergy misc Biology (General)
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title	TIGIT Marks Exhausted T Cells, Correlates with Disease Progression, and Serves as a Target for Immune Restoration in HIV and SIV Infection.
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title_full	TIGIT Marks Exhausted T Cells, Correlates with Disease Progression, and Serves as a Target for Immune Restoration in HIV and SIV Infection
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title_sort	tigit marks exhausted t cells, correlates with disease progression, and serves as a target for immune restoration in hiv and siv infection
callnumber	RC581-607
title_auth	TIGIT Marks Exhausted T Cells, Correlates with Disease Progression, and Serves as a Target for Immune Restoration in HIV and SIV Infection.
abstract	HIV infection induces phenotypic and functional changes to CD8+ T cells defined by the coordinated upregulation of a series of negative checkpoint receptors that eventually result in T cell exhaustion and failure to control viral replication. We report that effector CD8+ T cells during HIV infection in blood and SIV infection in lymphoid tissue exhibit higher levels of the negative checkpoint receptor TIGIT. Increased frequencies of TIGIT+ and TIGIT+ PD-1+ CD8+ T cells correlated with parameters of HIV and SIV disease progression. TIGIT remained elevated despite viral suppression in those with either pharmacological antiretroviral control or immunologically in elite controllers. HIV and SIV-specific CD8+ T cells were dysfunctional and expressed high levels of TIGIT and PD-1. Ex-vivo single or combinational antibody blockade of TIGIT and/or PD-L1 restored viral-specific CD8+ T cell effector responses. The frequency of TIGIT+ CD4+ T cells correlated with the CD4+ T cell total HIV DNA. These findings identify TIGIT as a novel marker of dysfunctional HIV-specific T cells and suggest TIGIT along with other checkpoint receptors may be novel curative HIV targets to reverse T cell exhaustion.
abstractGer	HIV infection induces phenotypic and functional changes to CD8+ T cells defined by the coordinated upregulation of a series of negative checkpoint receptors that eventually result in T cell exhaustion and failure to control viral replication. We report that effector CD8+ T cells during HIV infection in blood and SIV infection in lymphoid tissue exhibit higher levels of the negative checkpoint receptor TIGIT. Increased frequencies of TIGIT+ and TIGIT+ PD-1+ CD8+ T cells correlated with parameters of HIV and SIV disease progression. TIGIT remained elevated despite viral suppression in those with either pharmacological antiretroviral control or immunologically in elite controllers. HIV and SIV-specific CD8+ T cells were dysfunctional and expressed high levels of TIGIT and PD-1. Ex-vivo single or combinational antibody blockade of TIGIT and/or PD-L1 restored viral-specific CD8+ T cell effector responses. The frequency of TIGIT+ CD4+ T cells correlated with the CD4+ T cell total HIV DNA. These findings identify TIGIT as a novel marker of dysfunctional HIV-specific T cells and suggest TIGIT along with other checkpoint receptors may be novel curative HIV targets to reverse T cell exhaustion.
abstract_unstemmed	HIV infection induces phenotypic and functional changes to CD8+ T cells defined by the coordinated upregulation of a series of negative checkpoint receptors that eventually result in T cell exhaustion and failure to control viral replication. We report that effector CD8+ T cells during HIV infection in blood and SIV infection in lymphoid tissue exhibit higher levels of the negative checkpoint receptor TIGIT. Increased frequencies of TIGIT+ and TIGIT+ PD-1+ CD8+ T cells correlated with parameters of HIV and SIV disease progression. TIGIT remained elevated despite viral suppression in those with either pharmacological antiretroviral control or immunologically in elite controllers. HIV and SIV-specific CD8+ T cells were dysfunctional and expressed high levels of TIGIT and PD-1. Ex-vivo single or combinational antibody blockade of TIGIT and/or PD-L1 restored viral-specific CD8+ T cell effector responses. The frequency of TIGIT+ CD4+ T cells correlated with the CD4+ T cell total HIV DNA. These findings identify TIGIT as a novel marker of dysfunctional HIV-specific T cells and suggest TIGIT along with other checkpoint receptors may be novel curative HIV targets to reverse T cell exhaustion.
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title_short	TIGIT Marks Exhausted T Cells, Correlates with Disease Progression, and Serves as a Target for Immune Restoration in HIV and SIV Infection.
url	https://doi.org/10.1371/journal.ppat.1005349 https://doaj.org/article/98d1b0911eb74042a13b8e84449dee0c https://doaj.org/toc/1553-7366 https://doaj.org/toc/1553-7374
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author2Str	Tsuyoshi Fujita Gabriela M Webb Benjamin J Burwitz Helen L Wu Jason S Reed Katherine B Hammond Kiera L Clayton Naoto Ishii Mohamed Abdel-Mohsen Teri Liegler Brooks I Mitchell Frederick M Hecht Mario Ostrowski Cecilia M Shikuma Scott G Hansen Mark Maurer Alan J Korman Steven G Deeks Jonah B Sacha Lishomwa C Ndhlovu
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TIGIT Marks Exhausted T Cells, Correlates with Disease Progression, and Serves as a Target for Immune Restoration in HIV and SIV Infection.

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