{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:58:05Z","timestamp":1790762285742,"version":"4.1.0"},"reference-count":123,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2020,9,5]],"date-time":"2020-09-05T00:00:00Z","timestamp":1599264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AR042527"],"award-info":[{"award-number":["R01 AR042527"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL117913"],"award-info":[{"award-number":["R01 HL117913"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI108906"],"award-info":[{"award-number":["R01 AI108906"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 HL142068"],"award-info":[{"award-number":["R01 HL142068"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P01 HL129941"],"award-info":[{"award-number":["P01 HL129941"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI108891"],"award-info":[{"award-number":["R01 AI108891"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AG045779"],"award-info":[{"award-number":["R01 AG045779"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U19 AI057266"],"award-info":[{"award-number":["U19 AI057266"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AI129191"],"award-info":[{"award-number":["R01 AI129191"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The transcription factor T cell factor 1 (TCF1), a pioneer transcription factor as well as a downstream effector of WNT\/\u03b2-catenin signaling, is indispensable for T cell development in the thymus. Recent studies have highlighted the additional critical role of TCF1 in peripheral T cell responses to acute and chronic infections as well as cancer. Here, we review the regulatory functions of TCF1 in the differentiation of T follicular helper cells, memory T cells and recently described stem-like exhausted T cells, where TCF1 promotes less differentiated stem-like cell states by controlling common gene-regulatory networks. These studies also provide insights into the mechanisms of defective T cell responses in older individuals. We discuss alterations in TCF1 expression and related regulatory networks with age and their consequences for T cell responses to infections and vaccination. The increasing understanding of the pathways regulating TCF1 expression and function in aged T cells holds the promise of enabling the design of therapeutic interventions aiming at improving T cell responses in older individuals.<\/jats:p>","DOI":"10.3390\/ijms21186497","type":"journal-article","created":{"date-parts":[[2020,9,6]],"date-time":"2020-09-06T23:12:49Z","timestamp":1599433969000},"page":"6497","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":80,"title":["The Transcription Factor TCF1 in T Cell Differentiation and Aging"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5736-8170","authenticated-orcid":false,"given":"Chulwoo","family":"Kim","sequence":"first","affiliation":[{"name":"Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA 94305-5166, USA"},{"name":"Department of Medicine, Palo Alto Veterans Administration Healthcare System, Palo Alto, CA 94304, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5018-144X","authenticated-orcid":false,"given":"Jun","family":"Jin","sequence":"additional","affiliation":[{"name":"Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA 94305-5166, USA"},{"name":"Department of Medicine, Palo Alto Veterans Administration Healthcare System, Palo Alto, CA 94304, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelia M.","family":"Weyand","sequence":"additional","affiliation":[{"name":"Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA 94305-5166, USA"},{"name":"Department of Medicine, Palo Alto Veterans Administration Healthcare System, Palo Alto, CA 94304, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7670-1856","authenticated-orcid":false,"given":"J\u00f6rg J.","family":"Goronzy","sequence":"additional","affiliation":[{"name":"Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, CA 94305-5166, USA"},{"name":"Department of Medicine, Palo Alto Veterans Administration Healthcare System, Palo Alto, CA 94304, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1002\/j.1460-2075.1991.tb07928.x","article-title":"Identification and cloning of TCF-1, a T lymphocyte-specific transcription factor containing a sequence-specific HMG box","volume":"10","author":"Oosterwegel","year":"1991","journal-title":"EMBO J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1242\/dev.118.2.439","article-title":"Differential expression of the HMG box factors TCF-1 and LEF-1 during murine embryogenesis","volume":"118","author":"Oosterwegel","year":"1993","journal-title":"Development"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1038\/ncb2283","article-title":"Opposing effects of Tcf3 and Tcf1 control Wnt stimulation of embryonic stem cell self-renewal","volume":"13","author":"Yi","year":"2011","journal-title":"Nat. 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