Journal Article
. 2014 Jul; 10(7):e1004251.
doi: 10.1371/journal.ppat.1004251.

T-bet and Eomes are differentially linked to the exhausted phenotype of CD8+ T cells in HIV infection

Marcus Buggert 1 Johanna Tauriainen 1 Takuya Yamamoto 2 Juliet Frederiksen 3 Martin A Ivarsson 4 Jakob Michaëlsson 4 Ole Lund 3 Bo Hejdeman 5 Marianne Jansson 6 Anders Sönnerborg 7 Richard A Koup 2 Michael R Betts 8 Annika C Karlsson 1 
  • PMID: 25032686
  •     66 References
  •     138 citations


CD8(+) T cell exhaustion represents a major hallmark of chronic HIV infection. Two key transcription factors governing CD8(+) T cell differentiation, T-bet and Eomesodermin (Eomes), have previously been shown in mice to differentially regulate T cell exhaustion in part through direct modulation of PD-1. Here, we examined the relationship between these transcription factors and the expression of several inhibitory receptors (PD-1, CD160, and 2B4), functional characteristics and memory differentiation of CD8(+) T cells in chronic and treated HIV infection. The expression of PD-1, CD160, and 2B4 on total CD8(+) T cells was elevated in chronically infected individuals and highly associated with a T-bet(dim)Eomes(hi) expressional profile. Interestingly, both resting and activated HIV-specific CD8(+) T cells in chronic infection were almost exclusively T-bet(dim)Eomes(hi) cells, while CMV-specific CD8(+) T cells displayed a balanced expression pattern of T-bet and Eomes. The T-bet(dim)Eomes(hi) virus-specific CD8(+) T cells did not show features of terminal differentiation, but rather a transitional memory phenotype with poor polyfunctional (effector) characteristics. The transitional and exhausted phenotype of HIV-specific CD8(+) T cells was longitudinally related to persistent Eomes expression after antiretroviral therapy (ART) initiation. Strikingly, these characteristics remained stable up to 10 years after ART initiation. This study supports the concept that poor human viral-specific CD8(+) T cell functionality is due to an inverse expression balance between T-bet and Eomes, which is not reversed despite long-term viral control through ART. These results aid to explain the inability of HIV-specific CD8(+) T cells to control the viral replication post-ART cessation.

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TCF1+ hepatitis C virus-specific CD8+ T cells are maintained after cessation of chronic antigen stimulation.
Dominik Wieland, Janine Kemming, +7 authors, Robert Thimme.
Nat Commun, 2017 May 04; 8. PMID: 28466857    Free PMC article.
Highly Cited.
Transcriptional and epigenetic regulation of T cell hyporesponsiveness.
Renata M Pereira, Patrick G Hogan, Anjana Rao, Gustavo J Martinez.
J Leukoc Biol, 2017 Jun 14; 102(3). PMID: 28606939    Free PMC article.
The Transcription Factor NFAT1 Participates in the Induction of CD4+ T Cell Functional Exhaustion during Plasmodium yoelii Infection.
Rachel Y Ames, Li-Min Ting, +2 authors, Fernando Macian.
Infect Immun, 2017 Jun 21; 85(9). PMID: 28630062    Free PMC article.
Molecular Dissection of CD8+ T-Cell Dysfunction.
Chao Wang, Meromit Singer, Ana C Anderson.
Trends Immunol, 2017 Jul 01; 38(8). PMID: 28662970    Free PMC article.
Ageing and latent CMV infection impact on maturation, differentiation and exhaustion profiles of T-cell receptor gammadelta T-cells.
Martine J Kallemeijn, Anne Mieke H Boots, +5 authors, Anton W Langerak.
Sci Rep, 2017 Jul 16; 7(1). PMID: 28710491    Free PMC article.
IL-21 Receptor Signaling Is Essential for Optimal CD4+ T Cell Function and Control of Mycobacterium tuberculosis Infection in Mice.
Satyanarayana Swamy Cheekatla, Deepak Tripathi, +5 authors, Ramakrishna Vankayalapati.
J Immunol, 2017 Sep 01; 199(8). PMID: 28855309    Free PMC article.
Coinhibitory Receptor Expression and Immune Checkpoint Blockade: Maintaining a Balance in CD8+ T Cell Responses to Chronic Viral Infections and Cancer.
Isobel S Okoye, Michael Houghton, +2 authors, Shokrollah Elahi.
Front Immunol, 2017 Oct 17; 8. PMID: 29033936    Free PMC article.
HIV-Specific CD8+ T Cells Exhibit Reduced and Differentially Regulated Cytolytic Activity in Lymphoid Tissue.
Morgan A Reuter, Perla M Del Rio Estrada, +15 authors, Michael R Betts.
Cell Rep, 2017 Dec 21; 21(12). PMID: 29262326    Free PMC article.
Memory T Cell Proliferation before Hepatitis C Virus Therapy Predicts Antiviral Immune Responses and Treatment Success.
Gema Méndez-Lagares, Ding Lu, +10 authors, Dennis J Hartigan-O'Connor.
J Immunol, 2017 Dec 22; 200(3). PMID: 29263212    Free PMC article.
Forced expression of IL-7R promotes CD8 T cell cytotoxicity to self antigen.
YuFeng Peng.
PLoS One, 2017 Dec 23; 12(12). PMID: 29272267    Free PMC article.
T-cell Immunoglobulin and ITIM Domain Contributes to CD8+ T-cell Immunosenescence.
Yangzi Song, Beibei Wang, +9 authors, Hui Zeng.
Aging Cell, 2018 Jan 20; 17(2). PMID: 29349889    Free PMC article.
Human Immunodeficiency Virus Type-1 Elite Controllers Maintain Low Co-Expression of Inhibitory Receptors on CD4+ T Cells.
Kajsa Noyan, Son Nguyen, +2 authors, Marcus Buggert.
Front Immunol, 2018 Feb 07; 9. PMID: 29403500    Free PMC article.
Emergence of Polyfunctional Cytotoxic CD4+ T Cells in Mycobacterium avium Immune Reconstitution Inflammatory Syndrome in Human Immunodeficiency Virus-Infected Patients.
Denise C Hsu, Kimberly F Breglio, +12 authors, Irini Sereti.
Clin Infect Dis, 2018 Mar 15; 67(3). PMID: 29538651    Free PMC article.
T-cell Dysfunction in Glioblastoma: Applying a New Framework.
Karolina I Woroniecka, Kristen E Rhodin, +2 authors, Peter E Fecci.
Clin Cancer Res, 2018 Mar 30; 24(16). PMID: 29593027    Free PMC article.
Highly Cited. Review.
Limited immune surveillance in lymphoid tissue by cytolytic CD4+ T cells during health and HIV disease.
Marcus Buggert, Son Nguyen, +23 authors, Michael R Betts.
PLoS Pathog, 2018 Apr 14; 14(4). PMID: 29652923    Free PMC article.
Type I interferon signaling attenuates regulatory T cell function in viral infection and in the tumor microenvironment.
Arunakumar Gangaplara, Craig Martens, +8 authors, Ethan M Shevach.
PLoS Pathog, 2018 Apr 20; 14(4). PMID: 29672594    Free PMC article.
Adaptive NKG2C+CD57+ Natural Killer Cell and Tim-3 Expression During Viral Infections.
Hassen Kared, Serena Martelli, +8 authors, Anis Larbi.
Front Immunol, 2018 May 08; 9. PMID: 29731749    Free PMC article.
Exposure of Human CD8+ T Cells to Type-2 Cytokines Impairs Division and Differentiation and Induces Limited Polarization.
Annette Fox, Kim L Harland, Katherine Kedzierska, Anne Kelso.
Front Immunol, 2018 Jun 13; 9. PMID: 29892290    Free PMC article.
Kidney-infiltrating T cells in murine lupus nephritis are metabolically and functionally exhausted.
Jeremy S Tilstra, Lyndsay Avery, +6 authors, Mark J Shlomchik.
J Clin Invest, 2018 Aug 22; 128(11). PMID: 30130253    Free PMC article.
PD1 is expressed on exhausted T cells as well as virus specific memory CD8+ T cells in the bone marrow of myeloma patients.
Anne-Marit Sponaas, Rui Yang, +7 authors, Anders Sundan.
Oncotarget, 2018 Sep 04; 9(62). PMID: 30174794    Free PMC article.
Characterization of eomesodermin and T-bet expression by allostimulated CD8+ T cells of healthy volunteers and kidney transplant patients in relation to graft outcome.
A Perez-Gutierrez, D M Metes, +3 authors, M B Ezzelarab.
Clin Exp Immunol, 2018 Sep 25; 194(2). PMID: 30246373    Free PMC article.
Human breast tumor-infiltrating CD8+ T cells retain polyfunctionality despite PD-1 expression.
Colt A Egelston, Christian Avalos, +9 authors, Peter P Lee.
Nat Commun, 2018 Oct 18; 9(1). PMID: 30327458    Free PMC article.
Highly competent, non-exhausted CD8+ T cells continue to tightly control pathogen load throughout chronic Trypanosoma cruzi infection.
Angela D Pack, Matthew H Collins, Charles S Rosenberg, Rick L Tarleton.
PLoS Pathog, 2018 Nov 13; 14(11). PMID: 30419010    Free PMC article.
The Roles of Coinhibitory Receptors in Pathogenesis of Human Retroviral Infections.
Keiko Yasuma-Mitobe, Masao Matsuoka.
Front Immunol, 2018 Dec 13; 9. PMID: 30538707    Free PMC article.
Heterogeneity of HBV-Specific CD8+ T-Cell Failure: Implications for Immunotherapy.
Kathrin Heim, Christoph Neumann-Haefelin, Robert Thimme, Maike Hofmann.
Front Immunol, 2019 Oct 18; 10. PMID: 31620140    Free PMC article.
Autoreactive CD8+ T cell exhaustion distinguishes subjects with slow type 1 diabetes progression.
Alice E Wiedeman, Virginia S Muir, +13 authors, S Alice Long.
J Clin Invest, 2019 Dec 10; 130(1). PMID: 31815738    Free PMC article.
7-oxo-DHEA enhances impaired M. tuberculosis-specific T cell responses during HIV-TB coinfection.
María Belén Vecchione, Natalia Laufer, +3 authors, Maria Florencia Quiroga.
J Biomed Sci, 2020 Jan 08; 27(1). PMID: 31906962    Free PMC article.
Microenvironment-Dependent Gradient of CTL Exhaustion in the AE17sOVA Murine Mesothelioma Tumor Model.
Jennifer L Hope, Panagiota I Spantidea, +9 authors, Peter D Katsikis.
Front Immunol, 2020 Jan 31; 10. PMID: 31998326    Free PMC article.
T-cell exhaustion in HIV infection.
Craig Fenwick, Victor Joo, +4 authors, Giuseppe Pantaleo.
Immunol Rev, 2019 Dec 29; 292(1). PMID: 31883174    Free PMC article.
Use of Mass Cytometry to Profile Human T Cell Exhaustion.
Frances Winkler, Bertram Bengsch.
Front Immunol, 2020 Feb 11; 10. PMID: 32038613    Free PMC article.
Characterizing the Dysfunctional NK Cell: Assessing the Clinical Relevance of Exhaustion, Anergy, and Senescence.
Sean J Judge, William J Murphy, Robert J Canter.
Front Cell Infect Microbiol, 2020 Mar 03; 10. PMID: 32117816    Free PMC article.
PD-1/PD-L1 Pathway Modulates Macrophage Susceptibility to Mycobacterium tuberculosis Specific CD8+ T cell Induced Death.
Guadalupe Verónica Suarez, Claudia Del Carmen Melucci Ganzarain, +6 authors, Maria Florencia Quiroga.
Sci Rep, 2019 Jan 19; 9(1). PMID: 30655556    Free PMC article.
Platelet function in HIV plus dengue coinfection associates with reduced inflammation and milder dengue illness.
Eugenio D Hottz, Anna Cecíllia Quirino-Teixeira, +3 authors, Patrícia T Bozza.
Sci Rep, 2019 May 10; 9(1). PMID: 31068600    Free PMC article.
Identification and characterization of HIV-specific resident memory CD8+ T cells in human lymphoid tissue.
Marcus Buggert, Son Nguyen, +36 authors, Michael R Betts.
Sci Immunol, 2018 Jun 03; 3(24). PMID: 29858286    Free PMC article.
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The Effectiveness of Checkpoint Inhibitor Combinations and Administration Timing Can Be Measured by Granzyme B PET Imaging.
Benjamin M Larimer, Emily Bloch, +4 authors, Umar Mahmood.
Clin Cancer Res, 2018 Oct 18; 25(4). PMID: 30327313    Free PMC article.
Paradoxical effects of obesity on T cell function during tumor progression and PD-1 checkpoint blockade.
Ziming Wang, Ethan G Aguilar, +30 authors, Arta M Monjazeb.
Nat Med, 2018 Nov 14; 25(1). PMID: 30420753    Free PMC article.
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Neonatal influenza-specific effector CTLs retain elevated CD31 levels at the site of infection and have decreased IFN-γ production.
Adam J Fike, Ogan K Kumova, Virginie J Tardif, Alison J Carey.
J Leukoc Biol, 2018 Dec 12; 105(3). PMID: 30536476    Free PMC article.
Contrasting Roles of the PD-1 Signaling Pathway in Dendritic Cell-Mediated Induction and Regulation of HIV-1-Specific Effector T Cell Functions.
Tatiana M Garcia-Bates, Mariana L Palma, +5 authors, Robbie B Mailliard.
J Virol, 2018 Dec 14; 93(5). PMID: 30541848    Free PMC article.
Therapeutic Targeting of HIV Reservoirs: How to Give T Cells a New Direction.
Hongbing Yang, Zoë Wallace, Lucy Dorrell.
Front Immunol, 2018 Dec 20; 9. PMID: 30564246    Free PMC article.
High Levels of Eomes Promote Exhaustion of Anti-tumor CD8+ T Cells.
Jing Li, Yi He, +2 authors, Chen Dong.
Front Immunol, 2019 Jan 09; 9. PMID: 30619337    Free PMC article.
Roles, function and relevance of LAG3 in HIV infection.
Colin G Graydon, Allison L Balasko, Keith R Fowke.
PLoS Pathog, 2019 Jan 18; 15(1). PMID: 30653605    Free PMC article.
Prognostic value of CD8 + PD-1+ immune infiltrates and PDCD1 gene expression in triple negative breast cancer.
Joe Yeong, Jeffrey Chun Tatt Lim, +15 authors, Puay Hoon Tan.
J Immunother Cancer, 2019 Feb 08; 7(1). PMID: 30728081    Free PMC article.
Is There a Positive Side to T Cell Exhaustion?
Graham Pawelec.
Front Immunol, 2019 Feb 15; 10. PMID: 30761152    Free PMC article.
The Transcription Factor TCF1 Preserves the Effector Function of Exhausted CD8 T Cells During Chronic Viral Infection.
Yifei Wang, Jianjun Hu, +14 authors, Lifan Xu.
Front Immunol, 2019 Mar 01; 10. PMID: 30814995    Free PMC article.
Distinct phenotype and function of circulating Vδ1+ and Vδ2+ γδT-cells in acute and chronic hepatitis B.
Kyong-Mi Chang, Daniel Traum, +17 authors, Hepatitis B Research Network (HBRN).
PLoS Pathog, 2019 Apr 19; 15(4). PMID: 30998783    Free PMC article.
Equine arteritis virus long-term persistence is orchestrated by CD8+ T lymphocyte transcription factors, inhibitory receptors, and the CXCL16/CXCR6 axis.
Mariano Carossino, Pouya Dini, +5 authors, Udeni B R Balasuriya.
PLoS Pathog, 2019 Jul 30; 15(7). PMID: 31356622    Free PMC article.
Levels of Human Immunodeficiency Virus DNA Are Determined Before ART Initiation and Linked to CD8 T-Cell Activation and Memory Expansion.
Genevieve E Martin, Matthew Pace, +14 authors, John Frater.
J Infect Dis, 2019 Nov 30; 221(7). PMID: 31776569    Free PMC article.
Function of Human Tumor-Infiltrating Lymphocytes in Early-Stage Non-Small Cell Lung Cancer.
Shaun M O'Brien, Astero Klampatsa, +11 authors, Steven M Albelda.
Cancer Immunol Res, 2019 May 06; 7(6). PMID: 31053597    Free PMC article.
Some Aspects of CD8+ T-Cell Exhaustion Are Associated With Altered T-Cell Mitochondrial Features and ROS Content in HIV Infection.
Christian Deo T Deguit, Michelle Hough, +7 authors, Rachel L Rutishauser.
J Acquir Immune Defic Syndr, 2019 Sep 13; 82(2). PMID: 31513075    Free PMC article.
An antigen to remember: regulation of B cell memory in health and disease.
Aleta Pupovac, Kim L Good-Jacobson.
Curr Opin Immunol, 2017 Mar 21; 45. PMID: 28319732    Free PMC article.
CXCR6+ NK Cells in Human Fetal Liver and Spleen Possess Unique Phenotypic and Functional Capabilities.
Laura S Angelo, Lynn H Bimler, +2 authors, Silke Paust.
Front Immunol, 2019 Apr 04; 10. PMID: 30941128    Free PMC article.
CD8+ T-Cell Response to HIV Infection in the Era of Antiretroviral Therapy.
Federico Perdomo-Celis, Natalia A Taborda, Maria T Rugeles.
Front Immunol, 2019 Aug 27; 10. PMID: 31447862    Free PMC article.
Towards multiscale modeling of the CD8+ T cell response to viral infections.
Subhasish Baral, Rubesh Raja, Pramita Sen, Narendra M Dixit.
Wiley Interdiscip Rev Syst Biol Med, 2019 Feb 28; 11(4). PMID: 30811096    Free PMC article.
The hallmarks of CMV-specific CD8 T-cell differentiation.
Sara P H van den Berg, Iris N Pardieck, +4 authors, Ramon Arens.
Med Microbiol Immunol, 2019 Apr 17; 208(3-4). PMID: 30989333    Free PMC article.
Receptor signaling, transcriptional, and metabolic regulation of T cell exhaustion.
Mumtaz Y Balkhi.
Oncoimmunology, 2020 May 05; 9(1). PMID: 32363117    Free PMC article.
Elite control of HIV is associated with distinct functional and transcriptional signatures in lymphoid tissue CD8+ T cells.
Son Nguyen, Claire Deleage, +20 authors, Michael R Betts.
Sci Transl Med, 2019 Dec 20; 11(523). PMID: 31852798    Free PMC article.
The evolving role of T-bet in resistance to infection.
Gretchen Harms Pritchard, Ross M Kedl, Christopher A Hunter.
Nat Rev Immunol, 2019 Mar 09; 19(6). PMID: 30846856    Free PMC article.
Epitherapy and immune checkpoint blockade: using epigenetic reinvigoration of exhausted and dysfunctional T cells to reimburse immunotherapy response.
Isabella McGoverne, Jenny Dunn, +3 authors, Sudha Rao.
BMC Immunol, 2020 Apr 23; 21(1). PMID: 32316916    Free PMC article.
Targeting Nuclear LSD1 to Reprogram Cancer Cells and Reinvigorate Exhausted T Cells via a Novel LSD1-EOMES Switch.
Wen Juan Tu, Robert D McCuaig, +14 authors, Sudha Rao.
Front Immunol, 2020 Jul 03; 11. PMID: 32612611    Free PMC article.
[Tole of T cell exhaustion in inducing immune tolerance and preventing graft-versus-host disease].
J L Wang, M Z Han.
Zhonghua Xue Ye Xue Za Zhi, 2019 Mar 05; 40(2). PMID: 30831636    Free PMC article.
Delayed Expression of PD-1 and TIGIT on HIV-Specific CD8 T Cells in Untreated HLA-B*57:01 Individuals Followed from Early Infection.
Lydia Scharf, Johanna Tauriainen, +6 authors, Annika C Karlsson.
J Virol, 2020 May 01; 94(14). PMID: 32350076    Free PMC article.
Cancer and HIV-1 Infection: Patterns of Chronic Antigen Exposure.
Selena Vigano, Sara Bobisse, +2 authors, Alexandre Harari.
Front Immunol, 2020 Jul 28; 11. PMID: 32714330    Free PMC article.
IL-7 receptor alpha defines heterogeneity and signature of human effector memory CD8+ T cells in high dimensional analysis.
Min Sun Shin, Dongjoo Kim, +8 authors, Insoo Kang.
Cell Immunol, 2020 Jul 04; 355. PMID: 32619811    Free PMC article.
Selective Upregulation of CTLA-4 on CD8+ T Cells Restricted by HLA-B*35Px Renders them to an Exhausted Phenotype in HIV-1 infection.
Shokrollah Elahi, Shima Shahbaz, Stan Houston.
PLoS Pathog, 2020 Aug 08; 16(8). PMID: 32760139    Free PMC article.
Tobacco smoke and morphine alter peripheral and CNS inflammation following HIV infection in a humanized mouse model.
William D Cornwell, Uma Sriram, +8 authors, Yuri Persidsky.
Sci Rep, 2020 Aug 21; 10(1). PMID: 32814790    Free PMC article.
Engineering CAR T Cells to Target the HIV Reservoir.
Wenli Mu, Mayra A Carrillo, Scott G Kitchen.
Front Cell Infect Microbiol, 2020 Sep 10; 10. PMID: 32903563    Free PMC article.
PD-L1 Checkpoint Inhibition Narrows the Antigen-Specific T Cell Receptor Repertoire in Chronic Lymphocytic Choriomeningitis Virus Infection.
S Klein, D Ghersi, +3 authors, A R M Kraft.
J Virol, 2020 Jul 10; 94(18). PMID: 32641478    Free PMC article.
Generation of highly activated, antigen-specific tumor-infiltrating CD8+ T cells induced by a novel T cell-targeted immunotherapy.
Ava Vila-Leahey, Alecia MacKay, +3 authors, Marianne M Stanford.
Oncoimmunology, 2020 Sep 15; 9(1). PMID: 32923145    Free PMC article.
Multitarget Direct-Acting Antiviral Therapy Is Associated With Superior Immunologic Recovery in Patients Coinfected With Human Immunodeficiency Virus and Hepatitis C Virus.
Shikha Shrivastava, Manasa Bhatta, +8 authors, Eleanor Wilson.
Hepatol Commun, 2018 Dec 18; 2(12). PMID: 30556035    Free PMC article.
Immunological profile of an infant treated with integrase inhibitor from the neonatal period.
Lucia Taramasso, Chiara Dentone, +9 authors, Antonio Di Biagio.
J Virus Erad, 2019 Feb 26; 5(1). PMID: 30800427    Free PMC article.
Analysis of Co-inhibitory Receptor Expression in COVID-19 Infection Compared to Acute Plasmodium falciparum Malaria: LAG-3 and TIM-3 Correlate With T Cell Activation and Course of Disease.
Marissa Herrmann, Sophia Schulte, +7 authors, Julian Schulze Zur Wiesch.
Front Immunol, 2020 Sep 29; 11. PMID: 32983106    Free PMC article.
The CD38/NAD/SIRTUIN1/EZH2 Axis Mitigates Cytotoxic CD8 T Cell Function and Identifies Patients with SLE Prone to Infections.
Eri Katsuyama, Abel Suarez-Fueyo, +9 authors, George C Tsokos.
Cell Rep, 2020 Jan 09; 30(1). PMID: 31914379    Free PMC article.
Novel Strategies to Combat CMV-Related Cardiovascular Disease.
Elena Vasilieva, Sara Gianella, Michael L Freeman.
Pathog Immun, 2020 Oct 23; 5(1). PMID: 33089035    Free PMC article.
An atlas of immune cell exhaustion in HIV-infected individuals revealed by single-cell transcriptomics.
Shaobo Wang, Qiong Zhang, +3 authors, Tariq M Rana.
Emerg Microbes Infect, 2020 Sep 22; 9(1). PMID: 32954948    Free PMC article.
Mechanisms of CD8+ T cell-mediated suppression of HIV/SIV replication.
Julia Bergild McBrien, Nitasha A Kumar, Guido Silvestri.
Eur J Immunol, 2018 Feb 11; 48(6). PMID: 29427516    Free PMC article.
Antigenic Restimulation of Virus-Specific Memory CD8+ T Cells Requires Days of Lytic Protein Accumulation for Maximal Cytotoxic Capacity.
Stephen A Migueles, Daniel C Rogan, +15 authors, Mark Connors.
J Virol, 2020 Sep 11; 94(23). PMID: 32907983    Free PMC article.
The Cxxc1 subunit of the Trithorax complex directs epigenetic licensing of CD4+ T cell differentiation.
Masahiro Kiuchi, Atsushi Onodera, +8 authors, Toshinori Nakayama.
J Exp Med, 2021 Jan 13; 218(4). PMID: 33433611    Free PMC article.
Immune suppression in gliomas.
Matthew M Grabowski, Eric W Sankey, +4 authors, Peter E Fecci.
J Neurooncol, 2020 Jun 17; 151(1). PMID: 32542437    Free PMC article.
Peripheral natural killer cells in chronic hepatitis B patients display multiple molecular features of T cell exhaustion.
Marie Marotel, Marine Villard, +15 authors, Antoine Marçais.
Elife, 2021 Jan 29; 10. PMID: 33507150    Free PMC article.
Class I histone deacetylase inhibition promotes CD8 T cell activation in ovarian cancer.
Tyler R McCaw, Nidhi Goel, +5 authors, Rebecca C Arend.
Cancer Med, 2020 Dec 29; 10(2). PMID: 33369199    Free PMC article.
Increase of α-dicarbonyls in liver and receptor for advanced glycation end products on immune cells are linked to nonalcoholic fatty liver disease and liver cancer.
Nataliia Petriv, Lavinia Neubert, +16 authors, Tetyana Yevsa.
Oncoimmunology, 2021 Feb 26; 10(1). PMID: 33628620    Free PMC article.
Hypoxia-inducible factor activity promotes antitumor effector function and tissue residency by CD8+ T cells.
Ilkka Liikanen, Colette Lauhan, +11 authors, Ananda W Goldrath.
J Clin Invest, 2021 Apr 02; 131(7). PMID: 33792560    Free PMC article.
mTOR Modulates CD8+ T Cell Differentiation in Mice with Invasive Pulmonary Aspergillosis.
Hao Wang, Yu Xiao, +2 authors, Dawei Liu.
Open Life Sci, 2018 May 04; 13. PMID: 33817078    Free PMC article.
CD8+ T Cell Responses during HCV Infection and HCC.
Maike Hofmann, Catrin Tauber, Nina Hensel, Robert Thimme.
J Clin Med, 2021 Apr 04; 10(5). PMID: 33801203    Free PMC article.
Advances in Understanding the Roles of CD244 (SLAMF4) in Immune Regulation and Associated Diseases.
Lin Sun, Xiaokun Gang, +4 authors, Guixia Wang.
Front Immunol, 2021 Apr 13; 12. PMID: 33841431    Free PMC article.
Characterizing Hepatitis C Virus-Specific CD4+ T Cells Following Viral-Vectored Vaccination, Directly Acting Antivirals, and Spontaneous Viral Cure.
Felicity Hartnell, Ilaria Esposito, +10 authors, Paul Klenerman.
Hepatology, 2020 Feb 06; 72(5). PMID: 32012325    Free PMC article.
BRAF and MEK inhibition in melanoma patients enables reprogramming of tumor infiltrating lymphocytes.
Lukas Peiffer, Farnoush Farahpour, +9 authors, Jürgen C Becker.
Cancer Immunol Immunother, 2020 Dec 05; 70(6). PMID: 33275172    Free PMC article.
Dual CD4-based CAR T cells with distinct costimulatory domains mitigate HIV pathogenesis in vivo.
Colby R Maldini, Daniel T Claiborne, +15 authors, Todd M Allen.
Nat Med, 2020 Sep 02; 26(11). PMID: 32868878
Role of nuclear localization in the regulation and function of T-bet and Eomes in exhausted CD8 T cells.
Laura M McLane, Shin Foong Ngiow, +15 authors, E John Wherry.
Cell Rep, 2021 May 13; 35(6). PMID: 33979613    Free PMC article.
Epigenetic Features of HIV-Induced T-Cell Exhaustion Persist Despite Early Antiretroviral Therapy.
Genevieve E Martin, Debattama R Sen, +16 authors, John Frater.
Front Immunol, 2021 Jun 22; 12. PMID: 34149690    Free PMC article.
Distinct Immune Profiles of Exhausted Effector and Memory CD8+ T Cells in Individuals With Filarial Lymphedema.
Sacha Horn, Dennis Borrero-Wolff, +9 authors, Laura E Layland.
Front Cell Infect Microbiol, 2021 Sep 07; 11. PMID: 34485170    Free PMC article.
NK Cells in a Tug-of-War With Cancer: The Roles of Transcription Factors and Cytoskeleton.
E Hui Clarissa Lee, Darren Chen Pei Wong, Jeak Ling Ding.
Front Immunol, 2021 Oct 02; 12. PMID: 34594338    Free PMC article.
Elevated glycolysis imparts functional ability to CD8+ T cells in HIV infection.
Akm Nur-Ur Rahman, Jun Liu, +10 authors, Mario Ostrowski.
Life Sci Alliance, 2021 Sep 23; 4(11). PMID: 34548381    Free PMC article.
Inverted CD8 T-Cell Exhaustion and Co-Stimulation Marker Balance Differentiate Aviremic HIV-2-Infected From Seronegative Individuals.
Lydia Scharf, Christina B Pedersen, +12 authors, SWEGUB CORE Group.
Front Immunol, 2021 Oct 30; 12. PMID: 34712231    Free PMC article.
Human mucosal tissue-resident memory T cells in health and disease.
Joshua Lange, Olga Rivera-Ballesteros, Marcus Buggert.
Mucosal Immunol, 2021 Nov 08; 15(3). PMID: 34743182    Free PMC article.
Cyclophosphamide enhances the antitumor potency of GITR engagement by increasing oligoclonal cytotoxic T cell fitness.
Daniel Hirschhorn, Allison Betof Warner, +11 authors, Jedd D Wolchok.
JCI Insight, 2021 Oct 23; 6(20). PMID: 34676831    Free PMC article.
The TRAIL: TRAILshort Axis in HIV Immunopathology.
Fatma Aboulnasr, Geeta Paranjape, Andrew D Badley.
Crit Rev Immunol, 2018 Jan 01; 38(6). PMID: 31002603    Free PMC article.
The role of protease-activated receptor 1 signaling in CD8 T cell effector functions.
Hui Chen, Mindy Smith, +11 authors, Marta Catalfamo.
iScience, 2021 Nov 30; 24(11). PMID: 34841225    Free PMC article.
Differential Role of PD-1 Expressed by Various Immune and Tumor Cells in the Tumor Immune Microenvironment: Expression, Function, Therapeutic Efficacy, and Resistance to Cancer Immunotherapy.
Myeong Joon Kim, Sang-Jun Ha.
Front Cell Dev Biol, 2021 Dec 14; 9. PMID: 34901012    Free PMC article.
Colorectal Cancer-Associated Immune Exhaustion Involves T and B Lymphocytes and Conventional NK Cells and Correlates With a Shorter Overall Survival.
Carlo Sorrentino, Luigi D'Antonio, +2 authors, Emma Di Carlo.
Front Immunol, 2022 Jan 04; 12. PMID: 34975867    Free PMC article.
Single-Cell Sequencing Facilitates Elucidation of HIV Immunopathogenesis: A Review of Current Literature.
Silvere D Zaongo, Vijay Harypursat, Yaokai Chen.
Front Immunol, 2022 Feb 22; 13. PMID: 35185920    Free PMC article.
High Levels of CD244 Rather Than CD160 Associate With CD8+ T-Cell Aging.
Xinyue Wang, Di Wang, +9 authors, Yaxian Kong.
Front Immunol, 2022 Apr 08; 13. PMID: 35386693    Free PMC article.
HIV Infection Predisposes to Increased Chances of HBV Infection: Current Understanding of the Mechanisms Favoring HBV Infection at Each Clinical Stage of HIV Infection.
Silvere D Zaongo, Jing Ouyang, +3 authors, Yaokai Chen.
Front Immunol, 2022 Apr 19; 13. PMID: 35432307    Free PMC article.
Patients with HIV-associated cancers have evidence of increased T cell dysfunction and exhaustion prior to cancer diagnosis.
Omkar Chaudhary, Diane Trotta, +14 authors, Brinda Emu.
J Immunother Cancer, 2022 Apr 27; 10(4). PMID: 35470232    Free PMC article.
'Stem-like' precursors are the fount to sustain persistent CD8+ T cell responses.
Dietmar Zehn, Robert Thimme, +2 authors, Annette Oxenius.
Nat Immunol, 2022 May 28; 23(6). PMID: 35624209