{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T03:44:12Z","timestamp":1793159052403,"version":"4.5.0"},"reference-count":58,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T00:00:00Z","timestamp":1627257600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T00:00:00Z","timestamp":1627257600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/100000002","name":"U.S. Department of Health & Human Services | National Institutes of Health","doi-asserted-by":"publisher","award":["AI155577, AI105343, AI115712, AI117950, AI108545, AI082630 and CA210944"],"award-info":[{"award-number":["AI155577, AI105343, AI115712, AI117950, AI108545, AI082630 and CA210944"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Immunol"],"published-print":{"date-parts":[[2021,8]]},"DOI":"10.1038\/s41590-021-00975-5","type":"journal-article","created":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T12:05:31Z","timestamp":1627301131000},"page":"1008-1019","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":259,"title":["Epigenetic scarring of exhausted T cells hinders memory differentiation upon eliminating chronic antigenic stimulation"],"prefix":"10.1038","volume":"22","author":[{"given":"Mohamed S.","family":"Abdel-Hakeem","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sasikanth","family":"Manne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Christophe","family":"Beltra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erietta","family":"Stelekati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kito","family":"Nzingha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed-Alkhatim","family":"Ali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John L.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine R.","family":"Giles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Divij","family":"Mathew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison R.","family":"Greenplate","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Golnaz","family":"Vahedi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0477-1956","authenticated-orcid":false,"given":"E. John","family":"Wherry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,26]]},"reference":[{"key":"975_CR1","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1038\/nri3307","volume":"12","author":"SM Kaech","year":"2012","unstructured":"Kaech, S. M. & Cui, W. Transcriptional control of effector and memory CD8+ T cell differentiation. Nat. Rev. Immunol. 12, 749\u2013761 (2012).","journal-title":"Nat. Rev. Immunol."},{"key":"975_CR2","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1146\/annurev-immunol-041015-055318","volume":"37","author":"LM McLane","year":"2019","unstructured":"McLane, L. M., Abdel-Hakeem, M. S. & Wherry, E. J. CD8 T cell exhaustion during chronic viral infection and cancer. Annu. Rev. Immunol. 37, 457\u2013495 (2019).","journal-title":"Annu. Rev. Immunol."},{"key":"975_CR3","doi-asserted-by":"publisher","first-page":"4911","DOI":"10.1128\/JVI.77.8.4911-4927.2003","volume":"77","author":"EJ Wherry","year":"2003","unstructured":"Wherry, E. J., Blattman, J. N., Murali-Krishna, K., van der Most, R. & Ahmed, R. Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment. J. Virol. 77, 4911\u20134927 (2003).","journal-title":"J. Virol."},{"key":"975_CR4","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1016\/j.immuni.2007.09.006","volume":"27","author":"EJ Wherry","year":"2007","unstructured":"Wherry, E. J. et al. Molecular signature of CD8+ T cell exhaustion during chronic viral infection. Immunity 27, 670\u2013684 (2007).","journal-title":"Immunity"},{"key":"975_CR5","doi-asserted-by":"publisher","first-page":"477","DOI":"10.4049\/jimmunol.170.1.477","volume":"170","author":"MJ Fuller","year":"2003","unstructured":"Fuller, M. J. & Zajac, A. J. Ablation of CD8 and CD4 T cell responses by high viral loads. J. Immunol. 170, 477\u2013486 (2003).","journal-title":"J. Immunol."},{"key":"975_CR6","doi-asserted-by":"publisher","first-page":"16004","DOI":"10.1073\/pnas.0407192101","volume":"101","author":"EJ Wherry","year":"2004","unstructured":"Wherry, E. J., Barber, D. L., Kaech, S. M., Blattman, J. N. & Ahmed, R. Antigen-independent memory CD8 T cells do not develop during chronic viral infection. Proc. Natl Acad. Sci. USA 101, 16004\u201316009 (2004).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"975_CR7","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1084\/jem.20061937","volume":"204","author":"H Shin","year":"2007","unstructured":"Shin, H., Blackburn, S. D., Blattman, J. N. & Wherry, E. J. Viral antigen and extensive division maintain virus-specific CD8 T cells during chronic infection. J. Exp. Med. 204, 941\u2013949 (2007).","journal-title":"J. Exp. Med."},{"key":"975_CR8","doi-asserted-by":"publisher","first-page":"1523","DOI":"10.1084\/jem.20020066","volume":"195","author":"JT Tan","year":"2002","unstructured":"Tan, J. T. et al. Interleukin (IL)-15 and IL-7 jointly regulate homeostatic proliferation of memory phenotype CD8+ cells but are not required for memory phenotype CD4+ cells. J. Exp. Med. 195, 1523\u20131532 (2002).","journal-title":"J. Exp. Med."},{"key":"975_CR9","doi-asserted-by":"publisher","first-page":"1130","DOI":"10.1016\/j.immuni.2012.08.021","volume":"37","author":"TA Doering","year":"2012","unstructured":"Doering, T. A. et al. Network analysis reveals centrally connected genes and pathways involved in CD8+ T cell exhaustion versus memory. Immunity 37, 1130\u20131144 (2012).","journal-title":"Immunity"},{"key":"975_CR10","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.immuni.2014.01.005","volume":"40","author":"A Crawford","year":"2014","unstructured":"Crawford, A. et al. Molecular and transcriptional basis of CD4+ T cell dysfunction during chronic infection. Immunity 40, 289\u2013302 (2014).","journal-title":"Immunity"},{"key":"975_CR11","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1126\/science.aaf2807","volume":"354","author":"KE Pauken","year":"2016","unstructured":"Pauken, K. E. et al. Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade. Science 354, 1160\u20131165 (2016).","journal-title":"Science"},{"key":"975_CR12","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.1126\/science.aae0491","volume":"354","author":"DR Sen","year":"2016","unstructured":"Sen, D. R. et al. The epigenetic landscape of T cell exhaustion. Science 354, 1165\u20131169 (2016).","journal-title":"Science"},{"key":"975_CR13","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1038\/nature22367","volume":"545","author":"M Philip","year":"2017","unstructured":"Philip, M. et al. Chromatin states define tumour-specific T cell dysfunction and reprogramming. Nature 545, 452\u2013456 (2017).","journal-title":"Nature"},{"key":"975_CR14","doi-asserted-by":"publisher","first-page":"E2776","DOI":"10.1073\/pnas.1620498114","volume":"114","author":"GP Mognol","year":"2017","unstructured":"Mognol, G. P. et al. Exhaustion-associated regulatory regions in CD8+ tumor-infiltrating T cells. Proc. Natl Acad. Sci. USA 114, E2776\u2013E2785 (2017).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"975_CR15","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/j.immuni.2011.06.015","volume":"35","author":"B Youngblood","year":"2011","unstructured":"Youngblood, B. et al. Chronic virus infection enforces demethylation of the locus that encodes PD-1 in antigen-specific CD8+ T cells. Immunity 35, 400\u2013412 (2011).","journal-title":"Immunity"},{"key":"975_CR16","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.cell.2017.06.007","volume":"170","author":"HE Ghoneim","year":"2017","unstructured":"Ghoneim, H. E. et al. De novo epigenetic programs inhibit PD-1 blockade-mediated T cell rejuvenation. Cell 170, 142\u2013157.e19 (2017).","journal-title":"Cell"},{"key":"975_CR17","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1038\/s41586-019-1325-x","volume":"571","author":"O Khan","year":"2019","unstructured":"Khan, O. et al. TOX transcriptionally and epigenetically programs CD8+ T cell exhaustion. Nature 571, 211\u2013218 (2019).","journal-title":"Nature"},{"key":"975_CR18","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1038\/s41586-019-1326-9","volume":"571","author":"F Alfei","year":"2019","unstructured":"Alfei, F. et al. TOX reinforces the phenotype and longevity of exhausted T cells in chronic viral infection. Nature 571, 265\u2013269 (2019).","journal-title":"Nature"},{"key":"975_CR19","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1038\/s41586-019-1324-y","volume":"571","author":"AC Scott","year":"2019","unstructured":"Scott, A. C. et al. TOX is a critical regulator of tumour-specific T cell differentiation. Nature 571, 270\u2013274 (2019).","journal-title":"Nature"},{"key":"975_CR20","doi-asserted-by":"publisher","first-page":"890","DOI":"10.1038\/s41590-019-0403-4","volume":"20","author":"C Yao","year":"2019","unstructured":"Yao, C. et al. Single-cell RNA-seq reveals TOX as a key regulator of CD8+ T cell persistence in chronic infection. Nat. Immunol. 20, 890\u2013901 (2019).","journal-title":"Nat. Immunol."},{"key":"975_CR21","doi-asserted-by":"publisher","first-page":"12410","DOI":"10.1073\/pnas.1905675116","volume":"116","author":"H Seo","year":"2019","unstructured":"Seo, H. et al. TOX and TOX2 transcription factors cooperate with NR4A transcription factors to impose CD8+ T cell exhaustion. Proc. Natl Acad. Sci. USA 116, 12410\u201312415 (2019).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"975_CR22","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1016\/j.jhep.2019.05.015","volume":"71","author":"X Wang","year":"2019","unstructured":"Wang, X. et al. TOX promotes the exhaustion of antitumor CD8+ T cells by preventing PD1 degradation in hepatocellular carcinoma. J. Hepatol. 71, 731\u2013741 (2019).","journal-title":"J. Hepatol."},{"key":"975_CR23","doi-asserted-by":"publisher","first-page":"15016","DOI":"10.1073\/pnas.0801497105","volume":"105","author":"SD Blackburn","year":"2008","unstructured":"Blackburn, S. D., Shin, H., Freeman, G. J. & Wherry, E. J. Selective expansion of a subset of exhausted CD8 T cells by \u03b1PD-L1 blockade. Proc. Natl Acad. Sci. USA 105, 15016\u201315021 (2008).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"975_CR24","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.1126\/science.1229620","volume":"338","author":"MA Paley","year":"2012","unstructured":"Paley, M. A. et al. Progenitor and terminal subsets of CD8+ T cells cooperate to contain chronic viral infection. Science 338, 1220\u20131225 (2012).","journal-title":"Science"},{"key":"975_CR25","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/j.immuni.2016.07.021","volume":"45","author":"DT Utzschneider","year":"2016","unstructured":"Utzschneider, D. T. et al. T cell factor 1-expressing memory-like CD8+ T cells sustain the immune response to chronic viral infections. Immunity 45, 415\u2013427 (2016).","journal-title":"Immunity"},{"key":"975_CR26","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/nature19330","volume":"537","author":"SJ Im","year":"2016","unstructured":"Im, S. J. et al. Defining CD8+ T cells that provide the proliferative burst after PD-1 therapy. Nature 537, 417\u2013421 (2016).","journal-title":"Nature"},{"key":"975_CR27","doi-asserted-by":"publisher","first-page":"eaai8593","DOI":"10.1126\/sciimmunol.aai8593","volume":"1","author":"T Wu","year":"2016","unstructured":"Wu, T. et al. The TCF1-Bcl6 axis counteracts type I interferon to repress exhaustion and maintain T cell stemness. Sci. Immunol. 1, eaai8593 (2016).","journal-title":"Sci. Immunol."},{"key":"975_CR28","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1038\/nature19317","volume":"537","author":"R He","year":"2016","unstructured":"He, R. et al. Follicular CXCR5-expressing CD8+ T cells curtail chronic viral infection. Nature 537, 412\u2013428 (2016).","journal-title":"Nature"},{"key":"975_CR29","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1016\/j.immuni.2020.04.014","volume":"52","author":"JC Beltra","year":"2020","unstructured":"Beltra, J. C. et al. Developmental relationships of four exhausted CD8+ T cell subsets reveals underlying transcriptional and epigenetic landscape control mechanisms. Immunity 52, 825\u2013841.e8 (2020).","journal-title":"Immunity"},{"key":"975_CR30","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1016\/j.immuni.2019.11.002","volume":"51","author":"WH Hudson","year":"2019","unstructured":"Hudson, W. H. et al. Proliferating transitory T cells with an effector-like transcriptional signature emerge from PD-1+ stem-like CD8+ T cells during chronic infection. Immunity 51, 1043\u20131058.e4 (2019).","journal-title":"Immunity"},{"key":"975_CR31","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1016\/j.immuni.2019.10.009","volume":"51","author":"R Zander","year":"2019","unstructured":"Zander, R. et al. CD4+ T cell help is required for the formation of a cytolytic CD8+ T cell subset that protects against chronic infection and cancer. Immunity 51, 1028\u20131042.e4 (2019).","journal-title":"Immunity"},{"key":"975_CR32","doi-asserted-by":"publisher","first-page":"14113","DOI":"10.1073\/pnas.1903520116","volume":"116","author":"RR Jadhav","year":"2019","unstructured":"Jadhav, R. R. et al. Epigenetic signature of PD-1+ TCF1+ CD8 T cells that act as resource cells during chronic viral infection and respond to PD-1 blockade. Proc. Natl Acad. Sci. USA 116, 14113\u201314118 (2019).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"975_CR33","doi-asserted-by":"publisher","first-page":"8161","DOI":"10.1128\/JVI.00889-12","volume":"86","author":"JM Angelosanto","year":"2012","unstructured":"Angelosanto, J. M., Blackburn, S. D., Crawford, A. & Wherry, E. J. Progressive loss of memory T cell potential and commitment to exhaustion during chronic viral infection. J. Virol. 86, 8161\u20138170 (2012).","journal-title":"J. Virol."},{"key":"975_CR34","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1038\/ni.2606","volume":"14","author":"DT Utzschneider","year":"2013","unstructured":"Utzschneider, D. T. et al. T cells maintain an exhausted phenotype after antigen withdrawal and population reexpansion. Nat. Immunol. 14, 603\u2013610 (2013).","journal-title":"Nat. Immunol."},{"key":"975_CR35","doi-asserted-by":"publisher","first-page":"538","DOI":"10.1016\/j.jhep.2014.05.043","volume":"61","author":"B Martin","year":"2014","unstructured":"Martin, B. et al. Restoration of HCV-specific CD8+ T cell function by interferon-free therapy. J. Hepatol. 61, 538\u2013543 (2014).","journal-title":"J. Hepatol."},{"key":"975_CR36","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1111\/jvh.12465","volume":"22","author":"MA Burchill","year":"2015","unstructured":"Burchill, M. A., Golden-Mason, L., Wind-Rotolo, M. & Rosen, H. R. Memory re-differentiation and reduced lymphocyte activation in chronic HCV-infected patients receiving direct-acting antivirals. J. Viral Hepat. 22, 983\u2013991 (2015).","journal-title":"J. Viral Hepat."},{"key":"975_CR37","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms15050","volume":"8","author":"D Wieland","year":"2017","unstructured":"Wieland, D. et al. TCF1+ hepatitis C virus-specific CD8+ T cells are maintained after cessation of chronic antigen stimulation. Nat. Commun. 8, 15050 (2017).","journal-title":"Nat. Commun."},{"key":"975_CR38","doi-asserted-by":"publisher","first-page":"2599","DOI":"10.1056\/NEJMoa1512610","volume":"373","author":"JJ Feld","year":"2015","unstructured":"Feld, J. J. et al. Sofosbuvir and velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infection. N. Engl. J. Med. 373, 2599\u20132607 (2015).","journal-title":"N. Engl. J. Med."},{"key":"975_CR39","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1016\/S1470-2045(19)30388-2","volume":"20","author":"C Robert","year":"2019","unstructured":"Robert, C. et al. Pembrolizumab versus ipilimumab in advanced melanoma (KEYNOTE-006): post-hoc 5-year results from an open-label, multicentre, randomised, controlled, phase 3 study. Lancet Oncol. 20, 1239\u20131251 (2019).","journal-title":"Lancet Oncol."},{"key":"975_CR40","doi-asserted-by":"publisher","first-page":"1535","DOI":"10.1056\/NEJMoa1910836","volume":"381","author":"J Larkin","year":"2019","unstructured":"Larkin, J. et al. Five-year survival with combined nivolumab and ipilimumab in advanced melanoma. N. Engl. J. Med. 381, 1535\u20131546 (2019).","journal-title":"N. Engl. J. Med."},{"key":"975_CR41","doi-asserted-by":"publisher","first-page":"1843","DOI":"10.1002\/eji.1830171226","volume":"17","author":"H Pircher","year":"1987","unstructured":"Pircher, H. et al. Molecular analysis of the antigen receptor of virus-specific cytotoxic T cells and identification of a new V alpha family. Eur. J. Immunol. 17, 1843\u20131846 (1987).","journal-title":"Eur. J. Immunol."},{"key":"975_CR42","doi-asserted-by":"publisher","first-page":"1125","DOI":"10.1084\/jem.20142237","volume":"212","author":"PM Odorizzi","year":"2015","unstructured":"Odorizzi, P. M., Pauken, K. E., Paley, M. A., Sharpe, A. & Wherry, E. J. Genetic absence of PD-1 promotes accumulation of terminally differentiated exhausted CD8+ T cells. J. Exp. Med. 212, 1125\u20131137 (2015).","journal-title":"J. Exp. Med."},{"key":"975_CR43","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1084\/jem.20001021","volume":"195","author":"JN Blattman","year":"2002","unstructured":"Blattman, J. N. et al. Estimating the precursor frequency of naive antigen-specific CD8 T cells. J. Exp. Med. 195, 657\u2013664 (2002).","journal-title":"J. Exp. Med."},{"key":"975_CR44","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1038\/nmeth.4150","volume":"14","author":"X Qiu","year":"2017","unstructured":"Qiu, X. et al. Single-cell mRNA quantification and differential analysis with Census. Nat. Methods 14, 309\u2013315 (2017).","journal-title":"Nat. Methods"},{"key":"975_CR45","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1038\/s41590-019-0312-6","volume":"20","author":"BC Miller","year":"2019","unstructured":"Miller, B. C. et al. Subsets of exhausted CD8+ T cells differentially mediate tumor control and respond to checkpoint blockade. Nat. Immunol. 20, 326\u2013336 (2019).","journal-title":"Nat. Immunol."},{"key":"975_CR46","doi-asserted-by":"publisher","first-page":"1213","DOI":"10.1038\/nmeth.2688","volume":"10","author":"JD Buenrostro","year":"2013","unstructured":"Buenrostro, J. D., Giresi, P. G., Zaba, L. C., Chang, H. Y. & Greenleaf, W. J. Transposition of native chromatin for fast and sensitive epigenomic profiling of open chromatin, DNA-binding proteins and nucleosome position. Nat. Methods 10, 1213\u20131218 (2013).","journal-title":"Nat. Methods"},{"key":"975_CR47","doi-asserted-by":"publisher","first-page":"682","DOI":"10.1038\/nature04444","volume":"439","author":"DL Barber","year":"2006","unstructured":"Barber, D. L. et al. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature 439, 682\u2013687 (2006).","journal-title":"Nature"},{"key":"975_CR48","doi-asserted-by":"publisher","first-page":"1531","DOI":"10.1002\/hep.27278","volume":"60","author":"B Callendret","year":"2014","unstructured":"Callendret, B. et al. T-cell immunity and hepatitis C virus reinfection after cure of chronic hepatitis C with an interferon-free antiviral regimen in a chimpanzee. Hepatology 60, 1531\u20131540 (2014).","journal-title":"Hepatology"},{"key":"975_CR49","doi-asserted-by":"publisher","unstructured":"Tonnerre, P. et al. Differentiation of exhausted CD8+ T cells after termination of chronic antigen stimulation stops short of achieving functional T cell memory. Nat. Immunol. https:\/\/doi.org\/10.1038\/s41590-021-00982-6 (2021).","DOI":"10.1038\/s41590-021-00982-6"},{"key":"975_CR50","doi-asserted-by":"publisher","unstructured":"Sen, D. R. et al. Epigenetic scars of CD8+ T cell exhaustion persist after cure of chronic infection in humans. Nat. Immunol. https:\/\/doi.org\/10.1038\/s41590-021-00979-1 (2021).","DOI":"10.1038\/s41590-021-00979-1"},{"key":"975_CR51","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1038\/s41590-020-00817-w","volume":"22","author":"N Hensel","year":"2021","unstructured":"Hensel, N. et al. Memory-like HCV-specific CD8+ T cells retain a molecular scar after cure of chronic HCV infection. Nat. Immunol. 22, 229\u2013239 (2021).","journal-title":"Nat. Immunol."},{"key":"975_CR52","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1038\/nbt.4096","volume":"36","author":"A Butler","year":"2018","unstructured":"Butler, A. et al. Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat. Biotechnol. 36, 411\u2013420 (2018).","journal-title":"Nat. Biotechnol."},{"key":"975_CR53","doi-asserted-by":"publisher","first-page":"giz121","DOI":"10.1093\/gigascience\/giz121","volume":"8","author":"YC Chen","year":"2019","unstructured":"Chen, Y. C. et al. IKAP\u2014identifying K mAjor cell Population groups in single-cell RNA-sequencing analysis. Gigascience 8, giz121 (2019).","journal-title":"Gigascience"},{"key":"975_CR54","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09234-6","volume":"10","author":"Y Zhou","year":"2019","unstructured":"Zhou, Y. et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat. Commun. 10, 1523 (2019).","journal-title":"Nat. Commun."},{"key":"975_CR55","doi-asserted-by":"crossref","unstructured":"Hahne, F. & Ivanec, R. in Statistical Genomics: Methods and Protocols (eds Mathe, E. & Davis, S.) 335\u2013351 (Humana Press, 2016).","DOI":"10.1007\/978-1-4939-3578-9_16"},{"key":"975_CR56","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1038\/nbt.1630","volume":"28","author":"CY McLean","year":"2010","unstructured":"McLean, C. Y. et al. GREAT improves functional interpretation of cis-regulatory regions. Nat. Biotechnol. 28, 495\u2013501 (2010).","journal-title":"Nat. Biotechnol."},{"key":"975_CR57","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1016\/j.molcel.2010.05.004","volume":"38","author":"S Heinz","year":"2010","unstructured":"Heinz, S. et al. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol. Cell 38, 576\u2013589 (2010).","journal-title":"Mol. Cell"},{"key":"975_CR58","doi-asserted-by":"publisher","first-page":"eaav3262","DOI":"10.1126\/sciadv.aav3262","volume":"5","author":"K Zhang","year":"2019","unstructured":"Zhang, K., Wang, M., Zhao, Y. & Wang, W. Taiji: system-level identification of key transcription factors reveals transcriptional waves in mouse embryonic development. Sci. Adv. 5, eaav3262 (2019).","journal-title":"Sci. Adv."}],"updated-by":[{"DOI":"10.1038\/s41590-021-01057-2","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2021,9,29]],"date-time":"2021-09-29T00:00:00Z","timestamp":1632873600000}}],"container-title":["Nature Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41590-021-00975-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41590-021-00975-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41590-021-00975-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T13:10:20Z","timestamp":1635426620000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41590-021-00975-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,26]]},"references-count":58,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2021,8]]}},"alternative-id":["975"],"URL":"https:\/\/doi.org\/10.1038\/s41590-021-00975-5","relation":{},"ISSN":["1529-2908","1529-2916"],"issn-type":[{"value":"1529-2908","type":"print"},{"value":"1529-2916","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,26]]},"assertion":[{"value":"4 May 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 June 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 July 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 September 2021","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1038\/s41590-021-01057-2","URL":"https:\/\/doi.org\/10.1038\/s41590-021-01057-2","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"E.J.W. is a member of the Parker Institute for Cancer Immunotherapy. E.J.W. has consulting agreements with and\/or is on the scientific advisory board for Merck, Marengo Therapeutics, Janssen, Related Sciences, Synthekine and Surface Oncology. E.J.W. is a founder of Surface Oncology and Arsenal Biosciences. E.J.W. has a patent licensing agreement on the PD-1 pathway with Roche\/Genentech. The remaining authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}