{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T08:17:47Z","timestamp":1790756267194,"version":"4.1.0"},"reference-count":110,"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\/501100000024","name":"Gouvernement du Canada | Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["419228"],"award-info":[{"award-number":["419228"]}],"id":[{"id":"10.13039\/501100000024","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>CD8+ memory T (TM) cells play a critical role in immune defense against infection. Two common \u03b3-chain family cytokines, IL-2 and IL-7, although triggering the same mTORC1\u2013S6K pathway, distinctly induce effector T (TE) cells and TM cells, respectively, but the underlying mechanism(s) remains elusive. In this study, we generated IL-7R-\/and AMPK\u03b11-knockout (KO)\/OTI mice. By using genetic and pharmaceutical tools, we demonstrate that IL-7 deficiency represses expression of FOXO1, TCF1, p-AMPK\u03b11 (T172), and p-ULK1 (S555) and abolishes T cell memory differentiation in IL-7R KO T cells after Listeria monocytogenesis rLmOVA infection. IL-2\u2013 and IL-7\u2013stimulated strong and weak S6K (IL-2\/S6Kstrong and IL-7\/S6Kweak) signals control short-lived IL-7R\u2212CD62L\u2212KLRG1+ TE and long-term IL-7R+CD62L+KLRG1\u2212 TM cell formations, respectively. To assess underlying molecular pathway(s), we performed flow cytometry, Western blotting, confocal microscopy, and Seahorse assay analyses by using the IL-7\/S6Kweak\u2013stimulated TM (IL-7\/TM) and the control IL-2\/S6Kstrong\u2013stimulated TE (IL-2\/TE) cells. We determine that the IL-7\/S6Kweak signal activates transcriptional FOXO1, TCF1, and Id3 and metabolic p-AMPK\u03b11, p-ULK1, and ATG7 molecules in IL-7\/TM cells. IL-7\/TM cells upregulate IL-7R and CD62L, promote mitochondria biogenesis and fatty acid oxidation metabolism, and show long-term cell survival and functional recall responses. Interestingly, AMPK\u03b11 deficiency abolishes the AMPK\u03b11 but maintains the FOXO1 pathway and induces a metabolic switch from fatty acid oxidation to glycolysis in AMPK\u03b11 KO IL-7\/TM cells, leading to loss of cell survival and recall responses. Taken together, our data demonstrate that IL-7\u2013stimulated weak strength of mTORC1\u2013S6K signaling controls T cell memory via activation of transcriptional FOXO1\u2013TCF1\u2013Id3 and metabolic AMPK\u03b11\u2013ULK1\u2013ATG7 pathways. This (to our knowledge) novel finding provides a new mechanism for a distinct IL-2\/IL-7 stimulation model in T cell memory and greatly impacts vaccine development.<\/jats:p>","DOI":"10.4049\/jimmunol.2100452","type":"journal-article","created":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T19:25:31Z","timestamp":1638818731000},"page":"155-168","source":"Crossref","is-referenced-by-count":28,"title":["Prosurvival IL-7\u2013Stimulated Weak Strength of mTORC1-S6K Controls T Cell Memory via Transcriptional FOXO1\u2013TCF1\u2013Id3 and Metabolic AMPK\u03b11\u2013ULK1\u2013ATG7 Pathways"],"prefix":"10.1093","volume":"208","author":[{"given":"Aizhang","family":"Xu","sequence":"first","affiliation":[{"name":"Cancer Research, Saskatchewan Cancer Agency , Saskatoon, Saskatchewan,","place":["Canada"]},{"name":"Division of Oncology, College of Medicine, University of Saskatchewan , Saskatoon, Saskatchewan,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8488-7822","authenticated-orcid":false,"given":"Scot C","family":"Leary","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Microbiology and Immunology, College of Medicine, University of Saskatchewan , Saskatoon, Saskatchewan,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7519-2049","authenticated-orcid":false,"given":"Md Fahmid","family":"Islam","sequence":"additional","affiliation":[{"name":"Cancer Research, Saskatchewan Cancer Agency , Saskatoon, Saskatchewan,","place":["Canada"]},{"name":"Division of Oncology, College of Medicine, University of Saskatchewan , Saskatoon, Saskatchewan,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaojia","family":"Wu","sequence":"additional","affiliation":[{"name":"Cancer Research, Saskatchewan Cancer Agency , Saskatoon, Saskatchewan,","place":["Canada"]},{"name":"Division of Oncology, College of Medicine, University of Saskatchewan , Saskatoon, Saskatchewan,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalpana Kalyanasundaram","family":"Bhanumathy","sequence":"additional","affiliation":[{"name":"Cancer Research, Saskatchewan Cancer Agency , Saskatoon, Saskatchewan,","place":["Canada"]},{"name":"Division of Oncology, College of Medicine, University of Saskatchewan , Saskatoon, Saskatchewan,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6302-4849","authenticated-orcid":false,"given":"Anjuman","family":"Ara","sequence":"additional","affiliation":[{"name":"Cancer Research, Saskatchewan Cancer Agency , Saskatoon, Saskatchewan,","place":["Canada"]},{"name":"Division of Oncology, College of Medicine, University of Saskatchewan , Saskatoon, Saskatchewan,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajni","family":"Chibbar","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, College of Medicine, University of Saskatchewan , Saskatoon, Saskatchewan,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Fleywald","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, College of Medicine, University of Saskatchewan , Saskatoon, Saskatchewan,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6376-6036","authenticated-orcid":false,"given":"Khawaja Ashfaque","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Veterinary Pathology, Western College of Veterinary Medicine, University of Saskatchewan , Saskatoon, Saskatchewan,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jim","family":"Xiang","sequence":"additional","affiliation":[{"name":"Cancer Research, Saskatchewan Cancer Agency , Saskatoon, Saskatchewan,","place":["Canada"]},{"name":"Division of Oncology, College of Medicine, University of Saskatchewan , Saskatoon, Saskatchewan,","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,1,1]]},"reference":[{"key":"2025021008471838700_r1","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1146\/annurev-immunol-032414-112014","article-title":"T cell fate at the single-cell level","volume":"34","author":"Buchholz","year":"2016","journal-title":"Annu. Rev. Immunol."},{"key":"2025021008471838700_r2","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1189\/jlb.2HI0215-049RR","article-title":"Differential expression of mannose-6-phosphate receptor regulates T cell contraction","volume":"98","author":"Ahmed","year":"2015","journal-title":"J. Leukoc. Biol."},{"key":"2025021008471838700_r3","doi-asserted-by":"crossref","first-page":"3698","DOI":"10.1182\/blood-2002-02-0657","article-title":"Lack of proliferative capacity of human effector and memory T cells expressing killer cell lectinlike receptor G1 (KLRG1)","volume":"100","author":"Voehringer","year":"2002","journal-title":"Blood"},{"key":"2025021008471838700_r4","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.immuni.2007.07.010","article-title":"Inflammation directs memory precursor and short-lived effector CD8(+) T cell fates via the graded expression of T-bet transcription factor","volume":"27","author":"Joshi","year":"2007","journal-title":"Immunity"},{"key":"2025021008471838700_r5","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1084\/jem.20071641","article-title":"Functional and genomic profiling of effector CD8 T cell subsets with distinct memory fates","volume":"205","author":"Sarkar","year":"2008","journal-title":"J. Exp. Med."},{"key":"2025021008471838700_r6","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1038\/ni.3031","article-title":"Molecular regulation of effector and memory T cell differentiation","volume":"15","author":"Chang","year":"2014","journal-title":"Nat. Immunol."},{"key":"2025021008471838700_r7","doi-asserted-by":"crossref","first-page":"4677","DOI":"10.4049\/jimmunol.175.7.4677","article-title":"Recall proliferation potential of memory CD8+ T cells and antiviral protection","volume":"175","author":"Bachmann","year":"2005","journal-title":"J. Immunol."},{"key":"2025021008471838700_r8","doi-asserted-by":"crossref","first-page":"4686","DOI":"10.4049\/jimmunol.175.7.4686","article-title":"Functional properties and lineage relationship of CD8+ T cell subsets identified by expression of IL-7 receptor alpha and CD62L","volume":"175","author":"Bachmann","year":"2005","journal-title":"J. Immunol."},{"key":"2025021008471838700_r9","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1038\/44385","article-title":"Two subsets of memory T lymphocytes with distinct homing potentials and effector functions","volume":"401","author":"Sallusto","year":"1999","journal-title":"Nature"},{"key":"2025021008471838700_r10","doi-asserted-by":"crossref","first-page":"2692","DOI":"10.3389\/fimmu.2018.02692","article-title":"Defining memory CD8 T cell","volume":"9","author":"Martin","year":"2018","journal-title":"Front. Immunol."},{"key":"2025021008471838700_r11","doi-asserted-by":"crossref","first-page":"686","DOI":"10.3389\/fimmu.2014.00686","article-title":"mTOR links environmental signals to T cell fate decisions","volume":"5","author":"Chapman","year":"2015","journal-title":"Front. Immunol."},{"key":"2025021008471838700_r12","doi-asserted-by":"crossref","first-page":"180","DOI":"10.3389\/fimmu.2016.00180","article-title":"mTOR regulation of lymphoid cells in immunity to pathogens","volume":"7","author":"Keating","year":"2016","journal-title":"Front. Immunol."},{"key":"2025021008471838700_r13","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.immuni.2010.09.002","article-title":"The mammalian target of rapamycin: linking T cell differentiation, function, and metabolism","volume":"33","author":"Powell","year":"2010","journal-title":"Immunity"},{"key":"2025021008471838700_r14","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/nature08155","article-title":"mTOR regulates memory CD8 T-cell differentiation","volume":"460","author":"Araki","year":"2009","journal-title":"Nature"},{"key":"2025021008471838700_r15","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1172\/JCI69856","article-title":"Aptamer-targeted inhibition of mTOR in T cells enhances antitumor immunity","volume":"124","author":"Berezhnoy","year":"2014","journal-title":"J. Clin. Invest."},{"key":"2025021008471838700_r16","doi-asserted-by":"crossref","first-page":"3080","DOI":"10.4049\/jimmunol.1103365","article-title":"Regulating mammalian target of rapamycin to tune vaccination-induced CD8(+) T cell responses for tumor immunity","volume":"188","author":"Li","year":"2012","journal-title":"J. Immunol."},{"key":"2025021008471838700_r17","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.ebiom.2016.01.019","article-title":"Modulation of mTOR signalling triggers the formation of stem cell-like memory T cells","volume":"4","author":"Scholz","year":"2016","journal-title":"EBioMedicine"},{"key":"2025021008471838700_r18","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.jconrel.2017.02.034","article-title":"Low-dose controlled release of mTOR inhibitors maintains T cell plasticity and promotes central memory T cells","volume":"263","author":"Gammon","year":"2017","journal-title":"J. Control. Release"},{"key":"2025021008471838700_r19","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1172\/JCI77746","article-title":"mTORC1 and mTORC2 selectively regulate CD8+ T cell differentiation","volume":"125","author":"Pollizzi","year":"2015","journal-title":"J. Clin. Invest."},{"key":"2025021008471838700_r20","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1016\/j.immuni.2019.03.028","article-title":"The \u03b3c family of cytokines: basic biology to therapeutic ramifications","volume":"50","author":"Leonard","year":"2019","journal-title":"Immunity"},{"key":"2025021008471838700_r21","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.immuni.2009.11.012","article-title":"Interleukin-2 and inflammation induce distinct transcriptional programs that promote the differentiation of effector cytolytic T cells","volume":"32","author":"Pipkin","year":"2010","journal-title":"Immunity"},{"key":"2025021008471838700_r22","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.immuni.2009.11.010","article-title":"Prolonged interleukin-2Ralpha expression on virus-specific CD8+ T cells favors terminal-effector differentiation in vivo","volume":"32","author":"Kalia","year":"2010","journal-title":"Immunity"},{"key":"2025021008471838700_r23","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/80868","article-title":"Interleukin-7 mediates the homeostasis of na\u00efve and memory CD8 T cells in vivo","volume":"1","author":"Schluns","year":"2000","journal-title":"Nat. Immunol."},{"key":"2025021008471838700_r24","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1038\/ni1009","article-title":"Selective expression of the interleukin 7 receptor identifies effector CD8 T cells that give rise to long-lived memory cells","volume":"4","author":"Kaech","year":"2003","journal-title":"Nat. Immunol."},{"key":"2025021008471838700_r25","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1084\/jem.20061871","article-title":"Impaired CD8 T cell memory and CD4 T cell primary responses in IL-7R alpha mutant mice","volume":"204","author":"Osborne","year":"2007","journal-title":"J. Exp. Med."},{"key":"2025021008471838700_r26","first-page":"1027","article-title":"Effects of IL-7 on memory CD8 T cell homeostasis are influenced by the timing of therapy in mice","volume":"118","author":"Nanjappa","year":"2008","journal-title":"J. Clin. Invest."},{"key":"2025021008471838700_r27","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1182\/blood-2012-05-431718","article-title":"IL-7 and IL-15 instruct the generation of human memory stem T cells from naive precursors","volume":"121","author":"Cieri","year":"2013","journal-title":"Blood"},{"key":"2025021008471838700_r28","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.cell.2015.03.021","article-title":"IL-7-induced glycerol transport and TAG synthesis promotes memory CD8+ T cell longevity","volume":"161","author":"Cui","year":"2015","journal-title":"Cell"},{"key":"2025021008471838700_r29","doi-asserted-by":"crossref","first-page":"17011","DOI":"10.1038\/celldisc.2017.11","article-title":"mTORC1 regulates mannose-6-phosphate receptor transport and T-cell vulnerability to regulatory T cells by controlling kinesin KIF13A","volume":"3","author":"Ahmed","year":"2017","journal-title":"Cell Discov."},{"key":"2025021008471838700_r30","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1038\/s41423-018-0031-1","article-title":"Mannose-6-phosphate receptor: a novel regulator of T cell immunity","volume":"15","author":"Ara","year":"2018","journal-title":"Cell. Mol. Immunol."},{"key":"2025021008471838700_r31","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1038\/icb.2012.69","article-title":"IL-7 downregulates IL-7R\u03b1 expression in human CD8 T cells by two independent mechanisms","volume":"91","author":"Ghazawi","year":"2013","journal-title":"Immunol. Cell Biol."},{"key":"2025021008471838700_r32","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s13578-016-0098-2","article-title":"IL-15 signaling promotes adoptive effector T-cell survival and memory formation in irradiation-induced lymphopenia","volume":"6","author":"Xu","year":"2016","journal-title":"Cell Biosci."},{"key":"2025021008471838700_r33","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.immuni.2011.12.007","article-title":"Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development","volume":"36","author":"van der Windt","year":"2012","journal-title":"Immunity"},{"key":"2025021008471838700_r34","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1016\/j.celrep.2015.12.095","article-title":"Mammalian target of rapamycin complex 2 controls CD8 T cell memory differentiation in a Foxo1-dependent manner","volume":"14","author":"Zhang","year":"2016","journal-title":"Cell Rep."},{"key":"2025021008471838700_r35","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1097\/00130832-200212000-00004","article-title":"Cytokines and their role in lymphoid development, differentiation and homeostasis","volume":"2","author":"Hofmann","year":"2002","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"key":"2025021008471838700_r36","doi-asserted-by":"crossref","first-page":"7315","DOI":"10.4049\/jimmunol.172.12.7315","article-title":"Initial antigen encounter programs CD8+ T cells competent to develop into memory cells that are activated in an antigen-free, IL-7- and IL-15-rich environment","volume":"172","author":"Carrio","year":"2004","journal-title":"J. Immunol."},{"key":"2025021008471838700_r37","doi-asserted-by":"crossref","first-page":"2826","DOI":"10.3389\/fimmu.2018.02826","article-title":"transcriptional and epigenetic regulation of effector and memory CD8 T cell differentiation","volume":"9","author":"Chen","year":"2018","journal-title":"Front. Immunol."},{"key":"2025021008471838700_r38","doi-asserted-by":"crossref","first-page":"187","DOI":"10.4049\/jimmunol.1300331","article-title":"FoxO1 controls effector-to-memory transition and maintenance of functional CD8 T cell memory","volume":"191","author":"Tejera","year":"2013","journal-title":"J. Immunol."},{"key":"2025021008471838700_r39","doi-asserted-by":"crossref","first-page":"14858","DOI":"10.1073\/pnas.1404264111","article-title":"Tsc1 promotes the differentiation of memory CD8+ T cells via orchestrating the transcriptional and metabolic programs","volume":"111","author":"Shrestha","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025021008471838700_r40","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1038\/ni.2153","article-title":"Repression of the DNA-binding inhibitor Id3 by Blimp-1 limits the formation of memory CD8+ T cells","volume":"12","author":"Ji","year":"2011","journal-title":"Nat. Immunol."},{"key":"2025021008471838700_r41","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1084\/jem.20171584","article-title":"Sustained Id2 regulation of E proteins is required for terminal differentiation of effector CD8+ T cells","volume":"215","author":"Omilusik","year":"2018","journal-title":"J. Exp. Med."},{"key":"2025021008471838700_r42","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1038\/ni1268","article-title":"Effector and memory CD8+ T cell fate coupled by T-bet and eomesodermin. [Published erratum appears in 2006 Nat. Immunol. 7: 113.]","volume":"6","author":"Intlekofer","year":"2005","journal-title":"Nat. Immunol."},{"key":"2025021008471838700_r43","doi-asserted-by":"crossref","first-page":"E8865","DOI":"10.1073\/pnas.1618916114","article-title":"FOXO1 opposition of CD8+ T cell effector programming confers early memory properties and phenotypic diversity","volume":"114","author":"Delpoux","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025021008471838700_r44","doi-asserted-by":"crossref","first-page":"911","DOI":"10.4049\/jimmunol.1700595","article-title":"Differential requirements for Tcf1 long isoforms in CD8+ and CD4+ T cell responses to acute viral infection","volume":"199","author":"Gullicksrud","year":"2017","journal-title":"J. Immunol."},{"key":"2025021008471838700_r45","doi-asserted-by":"crossref","first-page":"11285","DOI":"10.1073\/pnas.1934283100","article-title":"Insulin-induced phosphorylation of FKHR (Foxo1) targets to proteasomal degradation","volume":"100","author":"Matsuzaki","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025021008471838700_r46","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1016\/j.molcel.2017.05.032","article-title":"AMPK: mechanisms of cellular energy sensing and restoration of metabolic balance","volume":"66","author":"Garcia","year":"2017","journal-title":"Mol. Cell"},{"key":"2025021008471838700_r47","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1038\/nature07976","article-title":"Autophagy regulates lipid metabolism","volume":"458","author":"Singh","year":"2009","journal-title":"Nature"},{"key":"2025021008471838700_r48","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1038\/nature08097","article-title":"Enhancing CD8 T-cell memory by modulating fatty acid metabolism","volume":"460","author":"Pearce","year":"2009","journal-title":"Nature"},{"key":"2025021008471838700_r49","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/ncb2152","article-title":"AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1","volume":"13","author":"Kim","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"2025021008471838700_r50","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1038\/ni.3025","article-title":"Autophagy is essential for effector CD8(+) T cell survival and memory formation","volume":"15","author":"Xu","year":"2014","journal-title":"Nat. Immunol."},{"key":"2025021008471838700_r51","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1016\/j.immuni.2016.10.017","article-title":"Constitutive glycolytic metabolism supports CD8+ T cell effector memory differentiation during viral infection","volume":"45","author":"Phan","year":"2016","journal-title":"Immunity"},{"key":"2025021008471838700_r52","doi-asserted-by":"crossref","first-page":"3609","DOI":"10.1172\/JCI90895","article-title":"Proteasome activity regulates CD8+ T lymphocyte metabolism and fate specification","volume":"127","author":"Widjaja","year":"2017","journal-title":"J. Clin. Invest."},{"key":"2025021008471838700_r53","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1038\/ni.2985","article-title":"Bcl-6 directly represses the gene program of the glycolysis pathway","volume":"15","author":"Oestreich","year":"2014","journal-title":"Nat. Immunol."},{"key":"2025021008471838700_r54","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1126\/science.aax0860","article-title":"T cells with dysfunctional mitochondria induce multimorbidity and premature senescence","volume":"368","author":"Desd\u00edn-Mic\u00f3","year":"2020","journal-title":"Science"},{"key":"2025021008471838700_r55","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.cmet.2005.05.004","article-title":"Metabolic control through the PGC-1 family of transcription coactivators","volume":"1","author":"Lin","year":"2005","journal-title":"Cell Metab."},{"key":"2025021008471838700_r56","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.cell.2017.08.018","article-title":"Mitochondrial priming by CD28","volume":"171","author":"Klein Geltink","year":"2017","journal-title":"Cell"},{"key":"2025021008471838700_r57","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.cell.2016.05.035","article-title":"mitochondrial dynamics controls t cell fate through metabolic programming","volume":"166","author":"Buck","year":"2016","journal-title":"Cell"},{"key":"2025021008471838700_r58","doi-asserted-by":"crossref","first-page":"1488","DOI":"10.1126\/science.283.5407.1488","article-title":"Oxidative phosphorylation at the fin de si\u00e8cle","volume":"283","author":"Saraste","year":"1999","journal-title":"Science"},{"key":"2025021008471838700_r59","doi-asserted-by":"crossref","first-page":"2404","DOI":"10.1016\/j.celrep.2018.07.101","article-title":"Mitochondrial complex I activity is required for maximal autophagy","volume":"24","author":"Thomas","year":"2018","journal-title":"Cell Rep."},{"key":"2025021008471838700_r60","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/j.immuni.2015.02.002","article-title":"Mitochondria in the regulation of innate and adaptive immunity","volume":"42","author":"Weinberg","year":"2015","journal-title":"Immunity"},{"key":"2025021008471838700_r61","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1038\/460041a","article-title":"Immunology: a metabolic switch to memory","volume":"460","author":"Prlic","year":"2009","journal-title":"Nature"},{"key":"2025021008471838700_r62","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.cmet.2015.11.002","article-title":"Mitochondrial membrane potential identifies cells with enhanced stemness for cellular therapy","volume":"23","author":"Sukumar","year":"2016","journal-title":"Cell Metab."},{"key":"2025021008471838700_r63","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1038\/nm.2446","article-title":"A human memory T cell subset with stem cell-like properties","volume":"17","author":"Gattinoni","year":"2011","journal-title":"Nat. Med."},{"key":"2025021008471838700_r64","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1186\/s13045-015-0214-5","article-title":"The roles of stem cell memory T cells in hematological malignancies","volume":"8","author":"Xu","year":"2015","journal-title":"J. Hematol. Oncol."},{"key":"2025021008471838700_r65","doi-asserted-by":"crossref","first-page":"16689","DOI":"10.1073\/pnas.0808997105","article-title":"Exploring regulatory mechanisms of CD8+ T cell contraction","volume":"105","author":"Prlic","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025021008471838700_r66","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1016\/j.celrep.2012.10.015","article-title":"Dissecting T cell contraction in vivo using a genetically encoded reporter of apoptosis","volume":"2","author":"Garrod","year":"2012","journal-title":"Cell Rep."},{"key":"2025021008471838700_r67","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1126\/science.290.5495.1354","article-title":"Regulation of antigen-specific CD8+ T cell homeostasis by perforin and interferon-gamma","volume":"290","author":"Badovinac","year":"2000","journal-title":"Science"},{"key":"2025021008471838700_r68","doi-asserted-by":"crossref","first-page":"2074","DOI":"10.4049\/jimmunol.179.4.2074","article-title":"Generation of CD8 T cell memory is regulated by IL-12","volume":"179","author":"Pearce","year":"2007","journal-title":"J. Immunol."},{"key":"2025021008471838700_r69","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/cmi.2008.18","article-title":"Defect of CD8+ memory T cells developed in absence of IL-12 priming for secondary expansion","volume":"5","author":"Ye","year":"2008","journal-title":"Cell. Mol. Immunol."},{"key":"2025021008471838700_r70","doi-asserted-by":"crossref","first-page":"2482","DOI":"10.4049\/jimmunol.1800795","article-title":"4-1BB regulates effector CD8 T cell accumulation in the lung tissue through a TRAF1-, mTOR-, and antigen-dependent mechanism to enhance tissue-resident memory T cell formation during respiratory influenza infection","volume":"202","author":"Zhou","year":"2019","journal-title":"J. Immunol."},{"key":"2025021008471838700_r71","doi-asserted-by":"crossref","first-page":"4627","DOI":"10.4049\/jimmunol.1201854","article-title":"GITR-dependent regulation of 4-1BB expression: implications for T cell memory and anti-4-1BB-induced pathology","volume":"190","author":"Lin","year":"2013","journal-title":"J. Immunol."},{"key":"2025021008471838700_r72","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1126\/science.290.5489.92","article-title":"Dynamics of T lymphocyte responses: intermediates, effectors, and memory cells","volume":"290","author":"Lanzavecchia","year":"2000","journal-title":"Science"},{"key":"2025021008471838700_r73","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1038\/nri959","article-title":"Progressive differentiation and selection of the fittest in the immune response","volume":"2","author":"Lanzavecchia","year":"2002","journal-title":"Nat. Rev. Immunol."},{"key":"2025021008471838700_r74","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1126\/science.1163612","article-title":"Different T cell receptor signals determine CD8+ memory versus effector development","volume":"323","author":"Teixeiro","year":"2009","journal-title":"Science"},{"key":"2025021008471838700_r75","doi-asserted-by":"crossref","first-page":"5797","DOI":"10.4049\/jimmunol.1300905","article-title":"Cutting edge: The signals for the generation of T cell memory are qualitatively different depending on TCR ligand strength","volume":"191","author":"Knudson","year":"2013","journal-title":"J. Immunol."},{"key":"2025021008471838700_r76","doi-asserted-by":"crossref","first-page":"617","DOI":"10.3389\/fimmu.2015.00617","article-title":"TCR signaling in T cell memory","volume":"6","author":"Daniels","year":"2015","journal-title":"Front. Immunol."},{"key":"2025021008471838700_r77","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1158\/2326-6066.CIR-17-0016","article-title":"The antitumor effects of vaccine-activated CD8+ T cells associate with weak TCR signaling and induction of stem-like memory T cells","volume":"5","author":"Wu","year":"2017","journal-title":"Cancer Immunol. Res."},{"key":"2025021008471838700_r78","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.4049\/jimmunol.1901167","article-title":"TCR signal strength and antigen affinity regulate CD8+ memory T cells","volume":"205","author":"Solouki","year":"2020","journal-title":"J. Immunol."},{"key":"2025021008471838700_r79","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/nature07657","article-title":"Complete but curtailed T-cell response to very low-affinity antigen","volume":"458","author":"Zehn","year":"2009","journal-title":"Nature"},{"key":"2025021008471838700_r80","doi-asserted-by":"crossref","first-page":"2838","DOI":"10.4049\/jimmunol.1500639","article-title":"Low-affinity memory CD8+ T cells mediate robust heterologous immunity","volume":"196","author":"Krummey","year":"2016","journal-title":"J. Immunol."},{"key":"2025021008471838700_r81","doi-asserted-by":"crossref","first-page":"e3000648","DOI":"10.1371\/journal.pbio.3000648","article-title":"Eomes broadens the scope of CD8 T-cell memory by inhibiting apoptosis in cells of low affinity","volume":"18","author":"Kavazovi\u0107","year":"2020","journal-title":"PLoS Biol."},{"key":"2025021008471838700_r82","doi-asserted-by":"crossref","first-page":"2987","DOI":"10.3389\/fimmu.2018.02987","article-title":"Regulation of effector and memory CD8 T cell differentiation by IL-2-A balancing act","volume":"9","author":"Kalia","year":"2018","journal-title":"Front. Immunol."},{"key":"2025021008471838700_r83","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1002\/eji.201243008","article-title":"AMPK\u03b11: a glucose sensor that controls CD8 T-cell memory","volume":"43","author":"Rolf","year":"2013","journal-title":"Eur. J. Immunol."},{"key":"2025021008471838700_r84","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.immuni.2011.09.009","article-title":"Opposing signals from the Bcl6 transcription factor and the interleukin-2 receptor generate T helper 1 central and effector memory cells","volume":"35","author":"Pepper","year":"2011","journal-title":"Immunity"},{"key":"2025021008471838700_r85","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/ni.2242","article-title":"Molecular mechanisms that control the expression and activity of Bcl-6 in TH1 cells to regulate flexibility with a TFH-like gene profile","volume":"13","author":"Oestreich","year":"2012","journal-title":"Nat. Immunol."},{"key":"2025021008471838700_r86","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/j.immuni.2012.02.012","article-title":"Interleukin-2 inhibits germinal center formation by limiting T follicular helper cell differentiation","volume":"36","author":"Ballesteros-Tato","year":"2012","journal-title":"Immunity"},{"key":"2025021008471838700_r87","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.immuni.2014.12.030","article-title":"The energy sensor AMPK regulates T cell metabolic adaptation and effector responses in vivo","volume":"42","author":"Blagih","year":"2015","journal-title":"Immunity"},{"key":"2025021008471838700_r88","doi-asserted-by":"crossref","first-page":"4187","DOI":"10.4049\/jimmunol.1100367","article-title":"The liver kinase B1 is a central regulator of T cell development, activation, and metabolism","volume":"187","author":"MacIver","year":"2011","journal-title":"J. Immunol."},{"key":"2025021008471838700_r89","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.molcel.2008.03.003","article-title":"AMPK phosphorylation of raptor mediates a metabolic checkpoint","volume":"30","author":"Gwinn","year":"2008","journal-title":"Mol. Cell"},{"key":"2025021008471838700_r90","doi-asserted-by":"crossref","first-page":"14336","DOI":"10.1073\/pnas.1221740110","article-title":"CD8 memory T cells have a bioenergetic advantage that underlies their rapid recall ability","volume":"110","author":"van der Windt","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025021008471838700_r91","doi-asserted-by":"crossref","first-page":"210","DOI":"10.4049\/jimmunol.170.1.210","article-title":"A role for Stat5 in CD8+ T cell homeostasis","volume":"170","author":"Kelly","year":"2003","journal-title":"J. Immunol."},{"key":"2025021008471838700_r92","doi-asserted-by":"crossref","first-page":"16601","DOI":"10.1073\/pnas.1003457107","article-title":"Differential effects of STAT5 and PI3K\/AKT signaling on effector and memory CD8 T-cell survival","volume":"107","author":"Hand","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025021008471838700_r93","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1158\/0008-5472.CAN-11-2187","article-title":"Activated STAT5 promotes long-lived cytotoxic CD8+ T cells that induce regression of autochthonous melanoma","volume":"72","author":"Grange","year":"2012","journal-title":"Cancer Res."},{"key":"2025021008471838700_r94","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20110892","article-title":"Regulation and function of ribosomal protein S6 kinase (S6K) within mTOR signalling networks","volume":"441","author":"Magnuson","year":"2012","journal-title":"Biochem. J."},{"key":"2025021008471838700_r95","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.cmet.2012.05.010","article-title":"p70S6 kinase phosphorylates AMPK on serine 491 to mediate leptin\u2019s effect on food intake","volume":"16","author":"Dagon","year":"2012","journal-title":"Cell Metab."},{"key":"2025021008471838700_r96","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.celrep.2012.02.007","article-title":"PI3K-Akt-mTORC1-S6K1\/2 axis controls Th17 differentiation by regulating Gfi1 expression and nuclear translocation of ROR\u03b3. [Published erratum appears in 2021 Cell Rep. 34: 10886.]","volume":"1","author":"Kurebayashi","year":"2012","journal-title":"Cell Rep."},{"key":"2025021008471838700_r97","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1158\/0008-5472.CAN-14-2789","article-title":"Targeting the eIF4F translation initiation complex: a critical nexus for cancer development","volume":"75","author":"Pelletier","year":"2015","journal-title":"Cancer Res."},{"key":"2025021008471838700_r98","doi-asserted-by":"crossref","first-page":"ra57","DOI":"10.1126\/scisignal.aad8463","article-title":"The 4E-BP-eIF4E axis promotes rapamycin-sensitive growth and proliferation in lymphocytes","volume":"9","author":"So","year":"2016","journal-title":"Sci. Signal."},{"key":"2025021008471838700_r99","doi-asserted-by":"crossref","first-page":"e0188112","DOI":"10.1371\/journal.pone.0188112","article-title":"Forced expression of IL-7R promotes CD8 T cell cytotoxicity to self antigen","volume":"12","author":"Peng","year":"2017","journal-title":"PLoS One"},{"key":"2025021008471838700_r100","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1158\/2159-8290.CD-17-0538","article-title":"Constitutive signaling from an engineered IL7 receptor promotes durable tumor elimination by tumor-redirected T cells","volume":"7","author":"Shum","year":"2017","journal-title":"Cancer Discov."},{"key":"2025021008471838700_r101","doi-asserted-by":"crossref","first-page":"6719","DOI":"10.4049\/jimmunol.0904089","article-title":"Distinct roles for IL-2 and IL-15 in the differentiation and survival of CD8+ effector and memory T cells","volume":"184","author":"Mitchell","year":"2010","journal-title":"J. Immunol."},{"key":"2025021008471838700_r102","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.immuni.2010.01.009","article-title":"Interleukin-2 tickles T cell memory","volume":"32","author":"Belz","year":"2010","journal-title":"Immunity"},{"key":"2025021008471838700_r103","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1146\/annurev.immunol.21.120601.140946","article-title":"CD45: a critical regulator of signaling thresholds in immune cells","volume":"21","author":"Hermiston","year":"2003","journal-title":"Annu. Rev. Immunol."},{"key":"2025021008471838700_r104","doi-asserted-by":"crossref","first-page":"4317","DOI":"10.4049\/jimmunol.0903781","article-title":"Different proliferative potential and migratory characteristics of human CD4+ regulatory T cells that express either CD45RA or CD45RO","volume":"184","author":"Booth","year":"2010","journal-title":"J. Immunol."},{"key":"2025021008471838700_r105","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.immuni.2013.07.013","article-title":"The transcription factor Foxo1 controls central-memory CD8+ T cell responses to infection","volume":"39","author":"Kim","year":"2013","journal-title":"Immunity"},{"key":"2025021008471838700_r106","doi-asserted-by":"crossref","first-page":"100989","DOI":"10.1016\/j.isci.2020.100989","article-title":"Homeostatic cytokines drive epigenetic reprogramming of activated T cells into a \u201cnaive-memory\u201d phenotype","volume":"23","author":"Frumento","year":"2020","journal-title":"iScience"},{"key":"2025021008471838700_r107","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/cmi.2017.115","article-title":"Metabolic control of T-cell immunity via epigenetic mechanisms","volume":"15","author":"Zhang","year":"2018","journal-title":"Cell. Mol. Immunol."},{"key":"2025021008471838700_r108","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/nri2274","article-title":"T-cell quality in memory and protection: implications for vaccine design. [Published erratum appears in 2008 Nat. Rev. Immunol. 8: 486.]","volume":"8","author":"Seder","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"2025021008471838700_r109","doi-asserted-by":"crossref","first-page":"937","DOI":"10.4049\/jimmunol.1601102","article-title":"Epigenetic networks regulate the transcriptional program in memory and terminally differentiated CD8+ T cells","volume":"198","author":"Rodriguez","year":"2017","journal-title":"J. Immunol."},{"key":"2025021008471838700_r110","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/s41577-019-0203-y","article-title":"Metabolic coordination of T cell quiescence and activation","volume":"20","author":"Chapman","year":"2020","journal-title":"Nat. Rev. Immunol."}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/208\/1\/155\/61189373\/ji2100452.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/208\/1\/155\/61189373\/ji2100452.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,10]],"date-time":"2025-02-10T08:48:12Z","timestamp":1739177292000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/208\/1\/155\/7924483"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,1]]},"references-count":110,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,1,1]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.2100452","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]]}}}