{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T17:23:49Z","timestamp":1784309029149,"version":"3.55.0"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2023,12,27]],"date-time":"2023-12-27T00:00:00Z","timestamp":1703635200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100006492","name":"HHS | NIH | NIAID | Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI137248"],"award-info":[{"award-number":["AI137248"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"HHS | NIH | NIAID | Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI138945"],"award-info":[{"award-number":["AI138945"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"HHS | NIH | NIAID | Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI055434"],"award-info":[{"award-number":["AI055434"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Following viral infection, CD4+ T cell differentiation is tightly regulated by cytokines and TCR signals. Although most activated CD4+ T cells express IL-2R\u03b1 after lymphocytic choriomeningtis virus infection, by day 3 postinfection, only half of activated T cells maintain expression. IL-2R\u03b1 at this time point distinguishes precursors for terminally differentiated Th1 cells (IL-2R\u03b1hi) from precursors for Tfh cells and memory T cells (IL-2R\u03b1lo) and is linked to strong TCR signals. In this study, we test whether TCR-dependent IL-2 links the TCR to CD4+ T cell differentiation. We employ a mixture of anti\u2013IL-2 Abs to neutralize IL-2 throughout the primary CD4+ T cell response to lymphocytic choriomeningitis virus infection in mice or only after the establishment of lineage-committed effector cells (day 3 postinfection). We report that IL-2 signals drive the formation of Th1 precursor cells in the early stages of the immune response and sustain Th1 responses during its later stages (after day 3). Effector-stage IL-2 also shapes the composition and function of resulting CD4+ memory T cells. Although IL-2 has been shown previously to drive Th1 differentiation by reducing the activity of the transcriptional repressor TCF-1, we found that sustained IL-2 signals were still required to drive optimal Th1 differentiation even in the absence of TCF-1. Therefore, we concluded that IL-2 plays a central role throughout the effector phase in regulating the balance between Th1 and Tfh effector and memory cells via mechanisms that are both dependent and independent of its role in modulating TCF-1 activity.<\/jats:p>","DOI":"10.4049\/jimmunol.2300570","type":"journal-article","created":{"date-parts":[[2023,12,27]],"date-time":"2023-12-27T14:47:42Z","timestamp":1703688462000},"page":"586-595","source":"Crossref","is-referenced-by-count":7,"title":["Effector-Phase IL-2 Signals Drive Th1 Effector and Memory Responses Dependently and Independently of TCF-1"],"prefix":"10.1093","volume":"212","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4065-1129","authenticated-orcid":false,"given":"Krystal R","family":"Charley","sequence":"first","affiliation":[{"name":"Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine , Salt Lake City, UT 84112"},{"name":"Huntsman Cancer Institute, University of Utah Health , Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew G","family":"Ramstead","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine , Salt Lake City, UT 84112"},{"name":"Huntsman Cancer Institute, University of Utah Health , Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5000-7361","authenticated-orcid":false,"given":"Joseph G","family":"Matous","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine , Salt Lake City, UT 84112"},{"name":"Huntsman Cancer Institute, University of Utah Health , Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohichi","family":"Kumaki","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine , Salt Lake City, UT 84112"},{"name":"Huntsman Cancer Institute, University of Utah Health , Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3335-9258","authenticated-orcid":false,"given":"Linda M","family":"Sircy","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine , Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J Scott","family":"Hale","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine , Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew A","family":"Williams","sequence":"additional","affiliation":[{"name":"Division of Microbiology and Immunology, Department of Pathology, University of Utah School of Medicine , Salt Lake City, UT 84112"},{"name":"Huntsman Cancer Institute, University of Utah Health , Salt Lake City, UT 84112"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,12,27]]},"reference":[{"key":"2025020405443645500_r1","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1111\/j.1365-2567.2010.03338.x","article-title":"Nature and nurture: T-cell receptor\u2013dependent and T-cell receptor\u2013independent differentiation cues in the selection of the memory T-cell pool","volume":"131","author":"Kim","year":"2010","journal-title":"Immunology"},{"key":"2025020405443645500_r2","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1111\/imcb.12272","article-title":"Development of circulating CD4+ T-cell memory","volume":"97","author":"Soon","year":"2019","journal-title":"Immunol. 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