{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:36:26Z","timestamp":1790840186685,"version":"4.1.0"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"7685","license":[{"start":{"date-parts":[[2017,12,13]],"date-time":"2017-12-13T00:00:00Z","timestamp":1513123200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2017,12,13]],"date-time":"2017-12-13T00:00:00Z","timestamp":1513123200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2017,12,21]]},"DOI":"10.1038\/nature25144","type":"journal-article","created":{"date-parts":[[2017,12,12]],"date-time":"2017-12-12T14:32:41Z","timestamp":1513089161000},"page":"404-409","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":470,"title":["Effector CD8 T cells dedifferentiate into long-lived memory cells"],"prefix":"10.1038","volume":"552","author":[{"given":"Ben","family":"Youngblood","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Scott","family":"Hale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haydn T.","family":"Kissick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eunseon","family":"Ahn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Wieland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Araki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin E.","family":"West","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hazem E.","family":"Ghoneim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiping","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pranay","family":"Dogra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl W.","family":"Davis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogumila T.","family":"Konieczny","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rustom","family":"Antia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafi","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,12,13]]},"reference":[{"key":"BFnature25144_CR1","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1111\/j.1749-6632.2009.05126.x","volume":"1183","author":"JJ Obar","year":"2010","unstructured":"Obar, J. J. & Lefran\u00e7ois, L. Memory CD8+ T cell differentiation. Ann. NY Acad. Sci. 1183, 251\u2013266 (2010)","journal-title":"Ann. NY Acad. Sci."},{"key":"BFnature25144_CR2","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1038\/nri2619","volume":"9","author":"R Ahmed","year":"2009","unstructured":"Ahmed, R., Bevan, M. J., Reiner, S. L. & Fearon, D. T. The precursors of memory: models and controversies. Nat. Rev. Immunol. 9, 662\u2013668 (2009)","journal-title":"Nat. Rev. Immunol."},{"key":"BFnature25144_CR3","doi-asserted-by":"publisher","first-page":"630","DOI":"10.1126\/science.1235454","volume":"340","author":"VR Buchholz","year":"2013","unstructured":"Buchholz, V. R. et al. Disparate individual fates compose robust CD8+ T cell immunity. Science 340, 630\u2013635 (2013)","journal-title":"Science"},{"key":"BFnature25144_CR4","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1126\/science.1235487","volume":"340","author":"C Gerlach","year":"2013","unstructured":"Gerlach, C. et al. Heterogeneous differentiation patterns of individual CD8+ T cells. Science 340, 635\u2013639 (2013)","journal-title":"Science"},{"key":"BFnature25144_CR5","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1016\/S0092-8674(02)01139-X","volume":"111","author":"SM Kaech","year":"2002","unstructured":"Kaech, S. M., Hemby, S., Kersh, E. & Ahmed, R. Molecular and functional profiling of memory CD8 T cell differentiation. Cell 111, 837\u2013851 (2002)","journal-title":"Cell"},{"key":"BFnature25144_CR6","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":"BFnature25144_CR7","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.immuni.2010.06.014","volume":"33","author":"TC Wirth","year":"2010","unstructured":"Wirth, T. C. et al. Repetitive antigen stimulation induces stepwise transcriptome diversification but preserves a core signature of memory CD8+ T cell differentiation. Immunity 33, 128\u2013140 (2010)","journal-title":"Immunity"},{"key":"BFnature25144_CR8","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.bbagrm.2008.10.004","volume":"1789","author":"X Dang","year":"2009","unstructured":"Dang, X., Raffler, N. A. & Ley, K. Transcriptional regulation of mouse L-selectin. Biochim. Biophys. Acta 1789, 146\u2013152 (2009)","journal-title":"Biochim. Biophys. Acta"},{"key":"BFnature25144_CR9","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1038\/nature04882","volume":"442","author":"CM Carlson","year":"2006","unstructured":"Carlson, C. M. et al. Kruppel-like factor 2 regulates thymocyte and T-cell migration. Nature 442, 299\u2013302 (2006)","journal-title":"Nature"},{"key":"BFnature25144_CR10","doi-asserted-by":"publisher","first-page":"1191","DOI":"10.1038\/ni1009","volume":"4","author":"SM Kaech","year":"2003","unstructured":"Kaech, S. M. et al. Selective expression of the interleukin 7 receptor identifies effector CD8 T cells that give rise to long-lived memory cells. Nat. Immunol. 4, 1191\u20131198 (2003)","journal-title":"Nat. Immunol."},{"key":"BFnature25144_CR11","doi-asserted-by":"publisher","first-page":"625","DOI":"10.1084\/jem.20071641","volume":"205","author":"S Sarkar","year":"2008","unstructured":"Sarkar, S. et al. Functional and genomic profiling of effector CD8 T cell subsets with distinct memory fates. J. Exp. Med. 205, 625\u2013640 (2008)","journal-title":"J. Exp. Med."},{"key":"BFnature25144_CR12","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.immuni.2007.07.010","volume":"27","author":"NS Joshi","year":"2007","unstructured":"Joshi, N. S. et al. Inflammation directs memory precursor and short-lived effector CD8+ T cell fates via the graded expression of T-bet transcription factor. Immunity 27, 281\u2013295 (2007)","journal-title":"Immunity"},{"key":"BFnature25144_CR13","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.immuni.2009.05.014","volume":"31","author":"RL Rutishauser","year":"2009","unstructured":"Rutishauser, R. L. et al. Transcriptional repressor Blimp-1 promotes CD8+ T cell terminal differentiation and represses the acquisition of central memory T cell properties. Immunity 31, 296\u2013308 (2009)","journal-title":"Immunity"},{"key":"BFnature25144_CR14","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/S1074-7613(00)80470-7","volume":"8","author":"K Murali-Krishna","year":"1998","unstructured":"Murali-Krishna, K. et al. Counting antigen-specific CD8 T cells: a reevaluation of bystander activation during viral infection. Immunity 8, 177\u2013187 (1998)","journal-title":"Immunity"},{"key":"BFnature25144_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":"BFnature25144_CR16","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/S0092-8674(00)81656-6","volume":"99","author":"M Okano","year":"1999","unstructured":"Okano, M., Bell, D. W., Haber, D. A. & Li, E. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99, 247\u2013257 (1999)","journal-title":"Cell"},{"key":"BFnature25144_CR17","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1038\/21208","volume":"399","author":"J Jacob","year":"1999","unstructured":"Jacob, J. & Baltimore, D. Modelling T-cell memory by genetic marking of memory T cells in vivo. Nature 399, 593\u2013597 (1999)","journal-title":"Nature"},{"key":"BFnature25144_CR18","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.1038\/ni1403","volume":"7","author":"MA Cannarile","year":"2006","unstructured":"Cannarile, M. A. et al. Transcriptional regulator Id2 mediates CD8+ T cell immunity. Nat. Immunol. 7, 1317\u20131325 (2006)","journal-title":"Nat. Immunol."},{"key":"BFnature25144_CR19","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1038\/ni.2158","volume":"12","author":"CY Yang","year":"2011","unstructured":"Yang, C. Y. et al. The transcriptional regulators Id2 and Id3 control the formation of distinct memory CD8+ T cell subsets. Nat. Immunol. 12, 1221\u20131229 (2011)","journal-title":"Nat. Immunol."},{"key":"BFnature25144_CR20","doi-asserted-by":"publisher","first-page":"1687","DOI":"10.1126\/science.1139393","volume":"315","author":"JT Chang","year":"2007","unstructured":"Chang, J. T. et al. Asymmetric T lymphocyte division in the initiation of adaptive immune responses. Science 315, 1687\u20131691 (2007)","journal-title":"Science"},{"key":"BFnature25144_CR21","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1038\/ni.2842","volume":"15","author":"J Arsenio","year":"2014","unstructured":"Arsenio, J. et al. Early specification of CD8+ T lymphocyte fates during adaptive immunity revealed by single-cell gene-expression analyses. Nat. Immunol. 15, 365\u2013372 (2014)","journal-title":"Nat. Immunol."},{"key":"BFnature25144_CR22","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1111\/imm.12074","volume":"139","author":"B Youngblood","year":"2013","unstructured":"Youngblood, B., Hale, J. S. & Ahmed, R. T-cell memory differentiation: insights from transcriptional signatures and epigenetics. Immunology 139, 277\u2013284 (2013)","journal-title":"Immunology"},{"key":"BFnature25144_CR23","doi-asserted-by":"publisher","first-page":"10631","DOI":"10.1073\/pnas.1524490113","volume":"113","author":"BLK Ladle","year":"2016","unstructured":"Ladle, B. L. K., et al. De novo DNA methylation by DNA methyltransferase 3a controls early effector CD8+ T -cell fate decisions following activation. Proc. Natl Acad. Sci. USA 113, 10631\u201310636 (2016)","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnature25144_CR24","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1016\/j.immuni.2011.03.017","volume":"34","author":"JT Chang","year":"2011","unstructured":"Chang, J. T. et al. Asymmetric proteasome segregation as a mechanism for unequal partitioning of the transcription factor T-bet during T lymphocyte division. Immunity 34, 492\u2013504 (2011)","journal-title":"Immunity"},{"key":"BFnature25144_CR25","doi-asserted-by":"publisher","unstructured":"Akondy R. S. et al. Origin and differentiation of human memory CD8 T cells after vaccination. Nature \n                    http:\/\/doi.org\/10.1038\/nature24633\n                    \n                   (2017)","DOI":"10.1038\/nature24633"},{"key":"BFnature25144_CR26","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":"BFnature25144_CR27","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1084\/jem.172.4.1043","volume":"172","author":"M Matloubian","year":"1990","unstructured":"Matloubian, M., Somasundaram, T., Kolhekar, S. R., Selvakumar, R. & Ahmed, R. Genetic basis of viral persistence: single amino acid change in the viral glycoprotein affects ability of lymphocytic choriomeningitis virus to persist in adult mice. J. Exp. Med. 172, 1043\u20131048 (1990)","journal-title":"J. Exp. Med."},{"key":"BFnature25144_CR28","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":"BFnature25144_CR29","doi-asserted-by":"publisher","first-page":"3821","DOI":"10.4049\/jimmunol.177.6.3821","volume":"177","author":"EN Kersh","year":"2006","unstructured":"Kersh, E. N. Impaired memory CD8 T cell development in the absence of methyl-CpG-binding domain protein 2. J. Immunol. 177, 3821\u20133826 (2006)","journal-title":"J. Immunol."},{"key":"BFnature25144_CR30","doi-asserted-by":"publisher","first-page":"4083","DOI":"10.4049\/jimmunol.176.7.4083","volume":"176","author":"EN Kersh","year":"2006","unstructured":"Kersh, E. N. et al. Rapid demethylation of the IFN-\u03b3 gene occurs in memory but not naive CD8 T cells. J. Immunol. 176, 4083\u20134093 (2006)","journal-title":"J. Immunol."},{"key":"BFnature25144_CR31","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1038\/342559a0","volume":"342","author":"H Pircher","year":"1989","unstructured":"Pircher, H., B\u00fcrki, K., Lang, R., Hengartner, H. & Zinkernagel, R. M. Tolerance induction in double specific T-cell receptor transgenic mice varies with antigen. Nature 342, 559\u2013561 (1989)","journal-title":"Nature"},{"key":"BFnature25144_CR32","doi-asserted-by":"publisher","first-page":"900","DOI":"10.1038\/nature02633","volume":"429","author":"M Kaneda","year":"2004","unstructured":"Kaneda, M. et al. Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting. Nature 429, 900\u2013903 (2004)","journal-title":"Nature"},{"key":"BFnature25144_CR33","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1006\/meth.2001.1268","volume":"25","author":"BN Trinh","year":"2001","unstructured":"Trinh, B. N., Long, T. I. & Laird, P. W. DNA methylation analysis by MethyLight technology. Methods 25, 456\u2013462 (2001)","journal-title":"Methods"},{"key":"BFnature25144_CR34","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1186\/1471-2105-10-232","volume":"10","author":"Y Xi","year":"2009","unstructured":"Xi, Y. & Li, W. BSMAP: whole genome bisulfite sequence MAPping program. BMC Bioinformatics 10, 232 (2009)","journal-title":"BMC Bioinformatics"},{"key":"BFnature25144_CR35","first-page":"e141","volume":"43","author":"H Wu","year":"2015","unstructured":"Wu, H. et al. Detection of differentially methylated regions from whole-genome bisulfite sequencing data without replicates. Nucleic Acids Res. 43, e141 (2015)","journal-title":"Nucleic Acids Res."},{"key":"BFnature25144_CR36","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1093\/bioinformatics\/btq033","volume":"26","author":"AR Quinlan","year":"2010","unstructured":"Quinlan, A. R. & Hall, I. M. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841\u2013842 (2010)","journal-title":"Bioinformatics"},{"key":"BFnature25144_CR37","doi-asserted-by":"publisher","first-page":"e69","DOI":"10.1093\/nar\/gku154","volume":"42","author":"H Feng","year":"2014","unstructured":"Feng, H., Conneely, K. N. & Wu, H. A Bayesian hierarchical model to detect differentially methylated loci from single nucleotide resolution sequencing data. Nucleic Acids Res. 42, e69 (2014)","journal-title":"Nucleic Acids Res."},{"key":"BFnature25144_CR38","doi-asserted-by":"publisher","first-page":"12112","DOI":"10.1074\/jbc.M801745200","volume":"283","author":"Y Furukawa","year":"2008","unstructured":"Furukawa, Y. et al. Identification of novel isoforms of mouse L-selectin with different carboxyl-terminal tails. J. Biol. Chem. 283, 12112\u201312119 (2008)","journal-title":"J. Biol. Chem."}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/nature25144.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/nature25144","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/doifinder\/10.1038\/nature25144","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"http:\/\/www.nature.com\/articles\/nature25144.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T14:10:35Z","timestamp":1684419035000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nature25144"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12,13]]},"references-count":38,"journal-issue":{"issue":"7685","published-print":{"date-parts":[[2017,12,21]]}},"alternative-id":["BFnature25144"],"URL":"https:\/\/doi.org\/10.1038\/nature25144","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.732291373.793562833","asserted-by":"object"}]},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12,13]]},"assertion":[{"value":"3 November 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 November 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 December 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}