{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T06:56:51Z","timestamp":1776495411654,"version":"3.51.2"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2019,11,1]],"date-time":"2019-11-01T00:00:00Z","timestamp":1572566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Neonates often develop poor immunity against intracellular pathogens. Because CD8+ T cells are essential for eliminating infectious agents, it is crucial to understand why they behave differently in early life. Previous studies in mice have demonstrated that neonatal CD8+ T cells fail to form memory because of an intrinsic propensity to differentiate into short-lived effectors. However, the underlying mechanisms remain undefined. We now show that neonatal CD8+ T cells exhibit higher glycolytic activity than adult CD8+ T cells postinfection, which may be due to age-related differences in Lin28b expression. Importantly, when glycolysis is pharmacologically inhibited, the impaired formation of neonatal memory CD8+ T cells can be restored. Collectively, these data suggest that neonatal CD8+ T cells are inherently biased toward undergoing glycolytic metabolism postinfection, which compromises their ability to develop into memory CD8+ T cells in early life.<\/jats:p>","DOI":"10.4049\/jimmunol.1900426","type":"journal-article","created":{"date-parts":[[2019,10,9]],"date-time":"2019-10-09T18:25:21Z","timestamp":1570645521000},"page":"2571-2576","source":"Crossref","is-referenced-by-count":30,"title":["Cutting Edge: Elevated Glycolytic Metabolism Limits the Formation of Memory CD8+ T Cells in Early Life"],"prefix":"10.1093","volume":"203","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5846-7269","authenticated-orcid":false,"given":"Cybelle","family":"Tabilas","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Cornell University , Ithaca, NY 14853"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0016-3136","authenticated-orcid":false,"given":"Jocelyn","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Indiana University , Indianapolis, IN 46202"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4231-6017","authenticated-orcid":false,"given":"Xiaojing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Molecular and Structural Biochemistry, North Carolina State University , Raleigh, NC 27695"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7766-3502","authenticated-orcid":false,"given":"Jason W","family":"Locasale","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Cancer Biology, Duke University , Durham, NC 27710"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norah L","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Cornell University , Ithaca, NY 14853"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian D","family":"Rudd","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Cornell University , Ithaca, NY 14853"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,11,15]]},"reference":[{"key":"2025030417544023700_r1","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/nm0102-54","article-title":"Respiratory syncytial virus infection suppresses lung CD8+ T-cell effector activity and peripheral CD8+ T-cell memory in the respiratory tract","volume":"8","author":"Chang","year":"2002","journal-title":"Nat. Med."},{"key":"2025030417544023700_r2","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S1074-7613(00)80469-0","article-title":"Massive expansion of antigen-specific CD8+ T cells during an acute virus infection","volume":"8","author":"Butz","year":"1998","journal-title":"Immunity"},{"key":"2025030417544023700_r3","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1126\/science.280.5361.227","article-title":"The numbers game for virus-specific CD8+ T cells","volume":"280","author":"Doherty","year":"1998","journal-title":"Science"},{"key":"2025030417544023700_r4","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S1074-7613(00)80470-7","article-title":"Counting antigen-specific CD8 T cells: a reevaluation of bystander activation during viral infection","volume":"8","author":"Murali-Krishna","year":"1998","journal-title":"Immunity"},{"key":"2025030417544023700_r5","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1534\/genetics.115.179176","article-title":"MicroRNAs and their targets are differentially regulated in adult and neonatal mouse CD8+ T cells","volume":"201","author":"Wissink","year":"2015","journal-title":"Genetics"},{"key":"2025030417544023700_r6","doi-asserted-by":"crossref","first-page":"177","DOI":"10.4049\/jimmunol.1400553","article-title":"Rapid proliferation and differentiation impairs the development of memory CD8+ T cells in early life","volume":"193","author":"Smith","year":"2014","journal-title":"J. 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Immunol."},{"key":"2025030417544023700_r10","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1084\/jem.129.2.431","article-title":"Tissue interaction in the development of thymus lymphocytes","volume":"129","author":"Owen","year":"1969","journal-title":"J. Exp. Med."},{"key":"2025030417544023700_r11","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1084\/jem.193.3.365","article-title":"The importation of hematogenous precursors by the thymus is a gated phenomenon in normal adult mice","volume":"193","author":"Foss","year":"2001","journal-title":"J. Exp. 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