{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T13:24:18Z","timestamp":1777728258251,"version":"3.51.4"},"reference-count":71,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100001117","name":"amfAR, The Foundation for AIDS Research","doi-asserted-by":"publisher","award":["109226-58-RGRL"],"award-info":[{"award-number":["109226-58-RGRL"]}],"id":[{"id":"10.13039\/100001117","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["UM1AI126611-01"],"award-info":[{"award-number":["UM1AI126611-01"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"Department of Health | National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1135851"],"award-info":[{"award-number":["1135851"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"Department of Health | National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1149990"],"award-info":[{"award-number":["1149990"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>In people with HIV (PWH) on antiretroviral therapy (ART), immune dysfunction persists, including elevated expression of immune checkpoint (IC) proteins on total and HIV-specific T cells. Reversing immune exhaustion is one strategy to enhance the elimination of HIV-infected cells that persist in PWH on ART. We aimed to evaluate whether blocking CTL-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), T cell Ig domain and mucin domain 3 (TIM-3), T cell Ig and ITIM domain (TIGIT) and lymphocyte activation gene-3 (LAG-3) alone or in combination would enhance HIV-specific CD4+ and CD8+ T cell function ex vivo. Intracellular cytokine staining was performed using human PBMCs from PWH on ART (n = 11) and expression of CD107a, IFN-\u03b3, TNF-\u03b1, and IL-2 was quantified with HIV peptides and Abs to IC. We found the following: 1) IC blockade enhanced the induction of CD107a and IL-2 but not IFN-\u03b3 and TNF-\u03b1 in response to Gag and Nef peptides; 2) the induction of CD107a and IL-2 was greatest with multiple combinations of two Abs; and 3) Abs to LAG-3, CTLA-4, and TIGIT in combinations showed synergistic induction of IL-2 in HIV-specific CD8+ and CD107a and IL-2 production in HIV-specific CD4+ and CD8+ T cells. These results demonstrate that the combination of Abs to LAG-3, CTLA-4, or TIGIT can increase the frequency of cells expressing CD107a and IL-2 that associated with cytotoxicity and survival of HIV-specific CD4+ and CD8+ T cells in PWH on ART. These combinations should be further explored for an HIV cure.<\/jats:p>","DOI":"10.4049\/jimmunol.2100367","type":"journal-article","created":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T22:25:31Z","timestamp":1640125531000},"page":"54-62","source":"Crossref","is-referenced-by-count":31,"title":["Combination Immune Checkpoint Blockade Enhances IL-2 and CD107a Production from HIV-Specific T Cells Ex Vivo in People Living with HIV on Antiretroviral Therapy"],"prefix":"10.1093","volume":"208","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5380-1114","authenticated-orcid":false,"given":"Chris Y","family":"Chiu","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judy J","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashanti I","family":"Dantanarayana","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ajantha","family":"Solomon","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9462-0662","authenticated-orcid":false,"given":"Vanessa A","family":"Evans","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7707-1972","authenticated-orcid":false,"given":"Rachel","family":"Pascoe","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3588-3814","authenticated-orcid":false,"given":"C\u00e9line","family":"Gubser","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3012-0009","authenticated-orcid":false,"given":"Lydie","family":"Trautman","sequence":"additional","affiliation":[{"name":"Vaccine and Gene Therapy Institute, Oregon Health & Science University , Beaverton, OR"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8153-1799","authenticated-orcid":false,"given":"R\u00e9mi","family":"Fromentin","sequence":"additional","affiliation":[{"name":"Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al , Montreal, Quebec,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9747-5018","authenticated-orcid":false,"given":"Nicolas","family":"Chomont","sequence":"additional","affiliation":[{"name":"Centre de Recherche du Centre Hospitalier de l\u2019Universit\u00e9 de Montr\u00e9al , Montreal, Quebec,","place":["Canada"]},{"name":"Department of Microbiology, Infectiology and Immunology, Faculty of Medicine, Universit\u00e9 de Montr\u00e9al , Montreal, Quebec,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1460-5572","authenticated-orcid":false,"given":"James H","family":"McMahon","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Monash University and the Alfred Hospital , Melbourne, Victoria,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1906-6945","authenticated-orcid":false,"given":"Paul U","family":"Cameron","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria,","place":["Australia"]},{"name":"Department of Infectious Diseases, Monash University and the Alfred Hospital , Melbourne, Victoria,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas A","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0330-8241","authenticated-orcid":false,"given":"Sharon R","family":"Lewin","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria,","place":["Australia"]},{"name":"Department of Infectious Diseases, Monash University and the Alfred Hospital , Melbourne, Victoria,","place":["Australia"]},{"name":"Victorian Infectious Diseases Service, The Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity , Melbourne, Victoria,","place":["Australia"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,1,1]]},"reference":[{"key":"2025021008472350600_r1","doi-asserted-by":"crossref","first-page":"e317","DOI":"10.1016\/S2352-3018(18)30039-0","article-title":"Barriers and strategies to achieve a cure for HIV","volume":"5","author":"Pitman","year":"2018","journal-title":"Lancet HIV"},{"key":"2025021008472350600_r2","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/s41586-019-1841-8","article-title":"Why and where an HIV cure is needed and how it might be achieved","volume":"576","author":"Ndung\u2019u","year":"2019","journal-title":"Nature"},{"key":"2025021008472350600_r3","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/nri3862","article-title":"Molecular and cellular insights into T cell exhaustion","volume":"15","author":"Wherry","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"2025021008472350600_r4","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1038\/nature05115","article-title":"PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression","volume":"443","author":"Day","year":"2006","journal-title":"Nature"},{"key":"2025021008472350600_r5","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1038\/nm1482","article-title":"Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction. [Published erratum appears in 2006 Nat. Med. 12: 1329.]","volume":"12","author":"Trautmann","year":"2006","journal-title":"Nat. Med."},{"key":"2025021008472350600_r6","doi-asserted-by":"crossref","first-page":"1246","DOI":"10.1038\/ni1515","article-title":"Upregulation of CTLA-4 by HIV-specific CD4+ T cells correlates with disease progression and defines a reversible immune dysfunction","volume":"8","author":"Kaufmann","year":"2007","journal-title":"Nat. Immunol."},{"key":"2025021008472350600_r7","doi-asserted-by":"crossref","first-page":"e0206256","DOI":"10.1371\/journal.pone.0206256","article-title":"Cardiac morbidity in HIV infection is associated with checkpoint inhibitor LAG-3 on CD4 T cells","volume":"13","author":"Pallikkuth","year":"2018","journal-title":"PLoS One"},{"key":"2025021008472350600_r8","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1089\/aid.2016.0324","article-title":"Early and delayed antiretroviral therapy results in comparable reductions in CD8+ T cell exhaustion marker expression","volume":"33","author":"Rutishauser","year":"2017","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"2025021008472350600_r9","doi-asserted-by":"crossref","first-page":"40354","DOI":"10.1038\/srep40354","article-title":"Perturbed CD8+ T cell TIGIT\/CD226\/PVR axis despite early initiation of antiretroviral treatment in HIV infected individuals","volume":"7","author":"Tauriainen","year":"2017","journal-title":"Sci. Rep."},{"key":"2025021008472350600_r10","doi-asserted-by":"crossref","first-page":"2763","DOI":"10.1084\/jem.20081398","article-title":"Tim-3 expression defines a novel population of dysfunctional T cells with highly elevated frequencies in progressive HIV-1 infection","volume":"205","author":"Jones","year":"2008","journal-title":"J. Exp. Med."},{"key":"2025021008472350600_r11","doi-asserted-by":"crossref","first-page":"3873","DOI":"10.4049\/jimmunol.1402176","article-title":"The upregulation of LAG-3 on T cells defines a subpopulation with functional exhaustion and correlates with disease progression in HIV-infected subjects","volume":"194","author":"Tian","year":"2015","journal-title":"J. Immunol"},{"key":"2025021008472350600_r12","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1182\/blood-2010-12-328070","article-title":"Responsiveness of HIV-specific CD4 T cells to PD-1 blockade","volume":"118","author":"Porichis","year":"2011","journal-title":"Blood"},{"key":"2025021008472350600_r13","doi-asserted-by":"crossref","first-page":"e1005349","DOI":"10.1371\/journal.ppat.1005349","article-title":"TIGIT marks exhausted T cells, correlates with disease progression, and serves as a target for immune restoration in HIV and SIV infection","volume":"12","author":"Chew","year":"2016","journal-title":"PLoS Pathog."},{"key":"2025021008472350600_r14","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.clim.2017.09.002","article-title":"Antibodies targeting BTLA or TIM-3 enhance HIV-1 specific T cell responses in combination with PD-1 blockade","volume":"183","author":"Grabmeier-Pfistershammer","year":"2017","journal-title":"Clin. Immunol."},{"key":"2025021008472350600_r15","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1093\/infdis\/jix191","article-title":"Clinical trial of the anti-PD-L1 antibody BMS-936559 in HIV-1 infected participants on suppressive antiretroviral therapy","volume":"215","author":"Gay","year":"2017","journal-title":"J. Infect. Dis."},{"key":"2025021008472350600_r16","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1093\/annonc\/mdx696","article-title":"Drastic decrease of the HIV reservoir in a patient treated with nivolumab for lung cancer","volume":"29","author":"Guihot","year":"2018","journal-title":"Ann. Oncol."},{"key":"2025021008472350600_r17","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1093\/annonc\/mdy259","article-title":"Inconsistent HIV reservoir dynamics and immune responses following anti-PD-1 therapy in cancer patients with HIV infection","volume":"29","author":"Scully","year":"2018","journal-title":"Ann. Oncol."},{"key":"2025021008472350600_r18","doi-asserted-by":"crossref","first-page":"e1973","DOI":"10.1093\/cid\/ciaa1530","article-title":"Impact of Anti\u2013PD-1 and Anti\u2013CTLA-4 on the Human Immunodeficiency Virus (HIV) Reservoir in People Living With HIV With Cancer on Antiretroviral Therapy: The AIDS Malignancy Consortium 095 Study","volume":"73","author":"Rasmussen","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"2025021008472350600_r19","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1056\/NEJMoa1504030","article-title":"Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma","volume":"373","author":"Larkin","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"2025021008472350600_r20","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1186\/s13046-019-1259-z","article-title":"Combination of CTLA-4 and PD-1 blockers for treatment of cancer","volume":"38","author":"Rotte","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"2025021008472350600_r21","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1159\/000500902","article-title":"On the horizon: targeting next-generation immune checkpoints for cancer treatment","volume":"64","author":"Tundo","year":"2019","journal-title":"Chemotherapy"},{"key":"2025021008472350600_r22","doi-asserted-by":"crossref","first-page":"3007","DOI":"10.4049\/jimmunol.1000156","article-title":"Regulation of virus-specific CD4+ T cell function by multiple costimulatory receptors during chronic HIV infection","volume":"185","author":"Kassu","year":"2010","journal-title":"J. Immunol."},{"key":"2025021008472350600_r23","doi-asserted-by":"crossref","first-page":"e01263-17","DOI":"10.1128\/JVI.01263-17","article-title":"Differential inhibitory receptor expression on t cells delineates functional capacities in chronic viral infection","volume":"91","author":"Teigler","year":"2017","journal-title":"J. Virol."},{"key":"2025021008472350600_r24","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.omtm.2019.07.008","article-title":"HIV-specific T cell responses are highly stable on antiretroviral therapy","volume":"15","author":"Xu","year":"2019","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"2025021008472350600_r25","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1097\/00002030-200201250-00004","article-title":"Persistent HIV-1-specific cellular responses despite prolonged therapeutic viral suppression","volume":"16","author":"Appay","year":"2002","journal-title":"AIDS"},{"key":"2025021008472350600_r26","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1186\/s12885-019-6145-8","article-title":"IFN-\u03b3 down-regulates the PD-1 expression and assist nivolumab in PD-1-blockade effect on CD8+ T-lymphocytes in pancreatic cancer","volume":"19","author":"Ding","year":"2019","journal-title":"BMC Cancer"},{"key":"2025021008472350600_r27","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1038\/s41467-019-08798-7","article-title":"PD-1 blockade potentiates HIV latency reversal ex vivo in CD4+ T cells from ART-suppressed individuals","volume":"10","author":"Fromentin","year":"2019","journal-title":"Nat. Commun."},{"key":"2025021008472350600_r28","doi-asserted-by":"crossref","first-page":"e0161779","DOI":"10.1371\/journal.pone.0161779","article-title":"Preclinical development of ipilimumab and nivolumab combination immunotherapy: mouse tumor models, in vitro functional studies, and cynomolgus macaque toxicology. [Published erratum appears in 2016 PLos One 11: e0167251.]","volume":"11","author":"Selby","year":"2016","journal-title":"PLoS One"},{"key":"2025021008472350600_r29","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3758\/BF03193146","article-title":"G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences","volume":"39","author":"Faul","year":"2007","journal-title":"Behav. Res. Methods"},{"key":"2025021008472350600_r30","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1172\/JCI80142","article-title":"Ex vivo analysis identifies effective HIV-1 latency-reversing drug combinations","volume":"125","author":"Laird","year":"2015","journal-title":"J. Clin. Invest."},{"key":"2025021008472350600_r31","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.4049\/jimmunol.1901191","article-title":"Combination immune checkpoint blockade to reverse HIV latency","volume":"204","author":"van der Sluis","year":"2020","journal-title":"J. Immunol."},{"key":"2025021008472350600_r32","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1056\/NEJMoa1910836","article-title":"Five-year survival with combined nivolumab and ipilimumab in advanced melanoma","volume":"381","author":"Larkin","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"2025021008472350600_r33","doi-asserted-by":"crossref","first-page":"4911","DOI":"10.1128\/JVI.77.8.4911-4927.2003","article-title":"Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment","volume":"77","author":"Wherry","year":"2003","journal-title":"J. Virol."},{"key":"2025021008472350600_r34","doi-asserted-by":"crossref","first-page":"4781","DOI":"10.1182\/blood-2005-12-4818","article-title":"HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells","volume":"107","author":"Betts","year":"2006","journal-title":"Blood"},{"key":"2025021008472350600_r35","doi-asserted-by":"crossref","first-page":"4565","DOI":"10.1073\/pnas.0610335104","article-title":"Impaired NFAT nuclear translocation results in split exhaustion of virus-specific CD8+ T cell functions during chronic viral infection","volume":"104","author":"Agnellini","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025021008472350600_r36","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1016\/j.immuni.2018.09.024","article-title":"Successful anti-PD-1 cancer immunotherapy requires T cell-dendritic cell crosstalk involving the cytokines IFN-\u03b3 and IL-12","volume":"49","author":"Garris","year":"2018","journal-title":"Immunity"},{"key":"2025021008472350600_r37","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1084\/jem.20061198","article-title":"Helper T cell IL-2 production is limited by negative feedback and STAT-dependent cytokine signals","volume":"204","author":"Villarino","year":"2007","journal-title":"J. Exp. Med."},{"key":"2025021008472350600_r38","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.4049\/jimmunol.166.2.1097","article-title":"Bystander activation of CD8+ T cells contributes to the rapid production of IFN-gamma in response to bacterial pathogens","volume":"166","author":"Lertmemongkolchai","year":"2001","journal-title":"J. Immunol."},{"key":"2025021008472350600_r39","doi-asserted-by":"crossref","first-page":"e0157175","DOI":"10.1371\/journal.pone.0157175","article-title":"Exposure of human CD4 T cells to IL-12 results in enhanced TCR-induced cytokine production, altered TCR signaling, and increased oxidative metabolism","volume":"11","author":"Vacaflores","year":"2016","journal-title":"PLoS One"},{"key":"2025021008472350600_r40","doi-asserted-by":"crossref","first-page":"e1003208","DOI":"10.1371\/journal.ppat.1003208","article-title":"The third signal cytokine IL-12 rescues the anti-viral function of exhausted HBV-specific CD8 T cells","volume":"9","author":"Schurich","year":"2013","journal-title":"PLoS Pathog."},{"key":"2025021008472350600_r41","doi-asserted-by":"crossref","first-page":"e142640","DOI":"10.1172\/jci.insight.142640","article-title":"HIV-specific T-cell responses reflect substantive in vivo interactions with infected cells despite long-term therapy","volume":"6","author":"Stevenson","year":"2021","journal-title":"JCI Insight"},{"key":"2025021008472350600_r42","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/1742-4690-10-31","article-title":"Molecular signatures of T-cell inhibition in HIV-1 infection","volume":"10","author":"Larsson","year":"2013","journal-title":"Retrovirology"},{"key":"2025021008472350600_r43","doi-asserted-by":"crossref","first-page":"838","DOI":"10.1002\/(SICI)1521-4141(199903)29:03<838::AID-IMMU838>3.0.CO;2-P","article-title":"CTLA4 ligation attenuates AP-1, NFAT and NF-kappaB activity in activated T cells","volume":"29","author":"Fraser","year":"1999","journal-title":"Eur. J. Immunol."},{"key":"2025021008472350600_r44","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.jim.2018.02.003","article-title":"Establishment of engineered cell-based assays mediating LAG3 and PD1 immune suppression enables potency measurement of blocking antibodies and assessment of signal transduction","volume":"456","author":"Bhagwat","year":"2018","journal-title":"J. Immunol. Methods"},{"key":"2025021008472350600_r45","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1093\/intimm\/dxy007","article-title":"Mechanistic peculiarities of activation-induced mobilization of cytotoxic effector proteins in human T cells","volume":"30","author":"Lettau","year":"2018","journal-title":"Int. Immunol."},{"key":"2025021008472350600_r46","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/cdd.2008.133","article-title":"Distinct requirements for activation-induced cell surface expression of preformed Fas\/CD95 ligand and cytolytic granule markers in T cells","volume":"16","author":"Kassahn","year":"2009","journal-title":"Cell Death Differ."},{"key":"2025021008472350600_r47","doi-asserted-by":"crossref","first-page":"9358","DOI":"10.1073\/pnas.93.18.9358","article-title":"A dynamic assembly of diverse transcription factors integrates activation and cell-type information for interleukin 2 gene regulation","volume":"93","author":"Rothenberg","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025021008472350600_r48","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.jim.2016.01.007","article-title":"Assessment of costimulation and coinhibition in a triple parameter T cell reporter line: Simultaneous measurement of NF-\u03baB, NFAT and AP-1","volume":"430","author":"Jutz","year":"2016","journal-title":"J. Immunol. Methods"},{"key":"2025021008472350600_r49","doi-asserted-by":"crossref","first-page":"e0140694","DOI":"10.1371\/journal.pone.0140694","article-title":"TIM-3 suppresses anti-CD3\/CD28-induced TCR activation and IL-2 expression through the NFAT signaling pathway","volume":"10","author":"Tomkowicz","year":"2015","journal-title":"PLoS One"},{"key":"2025021008472350600_r50","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/j.imbio.2012.01.012","article-title":"Down-regulation of interleukin-2 production by CD4(+) T cells expressing TIM-3 through suppression of NFAT dephosphorylation and AP-1 transcription","volume":"217","author":"Lee","year":"2012","journal-title":"Immunobiology"},{"key":"2025021008472350600_r51","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.immuni.2016.05.001","article-title":"Lag-3, Tim-3, and TIGIT: co-inhibitory receptors with specialized functions in immune regulation","volume":"44","author":"Anderson","year":"2016","journal-title":"Immunity"},{"key":"2025021008472350600_r52","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1078\/0171-2985-00283","article-title":"NFAT transcription factors control HIV-1 expression through a binding site downstream of TAR region","volume":"208","author":"Romanchikova","year":"2003","journal-title":"Immunobiology"},{"key":"2025021008472350600_r53","doi-asserted-by":"crossref","first-page":"4805","DOI":"10.1182\/blood-2010-11-317297","article-title":"Surface expression patterns of negative regulatory molecules identify determinants of virus-specific CD8+ T-cell exhaustion in HIV infection","volume":"117","author":"Yamamoto","year":"2011","journal-title":"Blood"},{"key":"2025021008472350600_r54","doi-asserted-by":"crossref","first-page":"e1005761","DOI":"10.1371\/journal.ppat.1005761","article-title":"CD4+ T cells expressing PD-1, TIGIT and LAG-3 contribute to HIV persistence during ART","volume":"12","author":"Fromentin","year":"2016","journal-title":"PLoS Pathog."},{"key":"2025021008472350600_r55","doi-asserted-by":"crossref","first-page":"e21","DOI":"10.1097\/QAI.0000000000002001","article-title":"PD-1+ and TIGIT+ CD4 T cells are associated with coronary artery calcium progression in HIV-infected treated adults","volume":"81","author":"Bowler","year":"2019","journal-title":"J. Acquir. Immune Defic. Syndr."},{"key":"2025021008472350600_r56","doi-asserted-by":"crossref","first-page":"971","DOI":"10.4049\/jimmunol.1701551","article-title":"Immune checkpoint blockade restores HIV-specific CD4 T cell help for NK cells","volume":"201","author":"Porichis","year":"2018","journal-title":"J. Immunol."},{"key":"2025021008472350600_r57","doi-asserted-by":"crossref","first-page":"5118","DOI":"10.4049\/jimmunol.1301992","article-title":"Ikaros imposes a barrier to CD8+ T cell differentiation by restricting autocrine IL-2 production","volume":"192","author":"O\u2019Brien","year":"2014","journal-title":"J. Immunol."},{"key":"2025021008472350600_r58","doi-asserted-by":"crossref","first-page":"7239","DOI":"10.1073\/pnas.0502393102","article-title":"HIV-1-specific IFN-gamma\/IL-2-secreting CD8 T cells support CD4-independent proliferation of HIV-1-specific CD8 T cells","volume":"102","author":"Zimmerli","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025021008472350600_r59","doi-asserted-by":"crossref","first-page":"3466","DOI":"10.1182\/blood-2012-04-422550","article-title":"Profound metabolic, functional, and cytolytic differences characterize HIV-specific CD8 T cells in primary and chronic HIV infection","volume":"120","author":"Trautmann","year":"2012","journal-title":"Blood"},{"key":"2025021008472350600_r60","doi-asserted-by":"crossref","first-page":"7668","DOI":"10.1128\/JVI.00513-09","article-title":"Strong ability of Nef-specific CD4+ cytotoxic T cells to suppress human immunodeficiency virus type 1 (HIV-1) replication in HIV-1-infected CD4+ T cells and macrophages","volume":"83","author":"Zheng","year":"2009","journal-title":"J. Virol."},{"key":"2025021008472350600_r61","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1093\/intimm\/dxh207","article-title":"CD25+ CD4+ T cells compete with naive CD4+ T cells for IL-2 and exploit it for the induction of IL-10 production","volume":"17","author":"Barthlott","year":"2005","journal-title":"Int. Immunol."},{"key":"2025021008472350600_r62","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1016\/j.immuni.2019.11.003","article-title":"PD-L1:CD80 cis-heterodimer triggers the co-stimulatory receptor CD28 while repressing the inhibitory PD-1 and CTLA-4 pathways","volume":"51","author":"Zhao","year":"2019","journal-title":"Immunity"},{"key":"2025021008472350600_r63","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1146\/annurev.immunol.26.021607.090331","article-title":"PD-1 and its ligands in tolerance and immunity","volume":"26","author":"Keir","year":"2008","journal-title":"Annu. Rev. Immunol."},{"key":"2025021008472350600_r64","doi-asserted-by":"crossref","first-page":"e02035-18","DOI":"10.1128\/JVI.02035-18","article-title":"Contrasting roles of the PD-1 signaling pathway in dendritic cell-mediated induction and regulation of HIV-1-specific effector T cell functions","volume":"93","author":"Garcia-Bates","year":"2019","journal-title":"J. Virol."},{"key":"2025021008472350600_r65","doi-asserted-by":"crossref","first-page":"2699","DOI":"10.1084\/jem.20082429","article-title":"TIMs: central regulators of immune responses","volume":"205","author":"Hafler","year":"2008","journal-title":"J. Exp. Med."},{"key":"2025021008472350600_r66","doi-asserted-by":"crossref","first-page":"e1007429","DOI":"10.1371\/journal.ppat.1007429","article-title":"Roles, function and relevance of LAG3 in HIV infection","volume":"15","author":"Graydon","year":"2019","journal-title":"PLoS Pathog."},{"key":"2025021008472350600_r67","doi-asserted-by":"crossref","first-page":"2508","DOI":"10.1128\/JVI.02034-13","article-title":"Differential impact of PD-1 and\/or interleukin-10 blockade on HIV-1-specific CD4 T cell and antigen-presenting cell functions","volume":"88","author":"Porichis","year":"2014","journal-title":"J. Virol."},{"key":"2025021008472350600_r68","doi-asserted-by":"crossref","first-page":"e42","DOI":"10.1016\/S2352-3018(20)30234-4","article-title":"Multi-stakeholder consensus on a target product profile for an HIV cure","volume":"8","author":"Lewin","year":"2021","journal-title":"Lancet HIV"},{"key":"2025021008472350600_r69","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1016\/j.jhep.2019.06.028","article-title":"Anti-PD-1 blockade with nivolumab with and without therapeutic vaccination for virally suppressed chronic hepatitis B: a pilot study","volume":"71","author":"Gane","year":"2019","journal-title":"J. Hepatol."},{"key":"2025021008472350600_r70","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s13045-018-0582-8","article-title":"Next generation of immune checkpoint therapy in cancer: new developments and challenges","volume":"11","author":"Marin-Acevedo","year":"2018","journal-title":"J. Hematol. Oncol."},{"key":"2025021008472350600_r71","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1186\/s12943-019-1091-2","article-title":"Novel immune checkpoint targets: moving beyond PD-1 and CTLA-4","volume":"18","author":"Qin","year":"2019","journal-title":"Mol. Cancer"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/208\/1\/54\/61189572\/ji2100367.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/208\/1\/54\/61189572\/ji2100367.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T08:48:15Z","timestamp":1739177295000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/208\/1\/54\/7924500"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,1]]},"references-count":71,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.2100367","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,1]]},"published":{"date-parts":[[2022,1,1]]}}}