{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T17:10:49Z","timestamp":1791047449908,"version":"4.1.0"},"reference-count":28,"publisher":"National Academy of Sciences","issue":"21","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,5,25]]},"abstract":"<jats:p>Immune protection from intracellular pathogens depends on the generation of terminally differentiated effector and of multipotent memory precursor CD8 T cells, which rapidly regenerate effector and memory cells during recurrent infection. The identification of factors and pathways involved in CD8 T cell differentiation is of obvious importance to improve vaccination strategies. Here, we show that mice lacking T cell factor 1 (Tcf-1), a nuclear effector of the canonical Wingless\/Integration 1 (Wnt) signaling pathway, mount normal effector and effector memory CD8 T cell responses to infection with lymphocytic choriomeningitis virus (LCMV). However, Tcf-1\u2013deficient CD8 T cells are selectively impaired in their ability to expand upon secondary challenge and to protect from recurrent virus infection. Tcf-1\u2013deficient mice essentially lack CD8 memory precursor T cells, which is evident already at the peak of the primary response, suggesting that Tcf-1 programs CD8 memory cell fate. The function of Tcf-1 to establish CD8 T cell memory is dependent on the catenin-binding domain in Tcf-1 and requires the Tcf-1 coactivators and Wnt signaling intermediates \u03b2-catenin and \u03b3-catenin. These findings demonstrate that the canonical Wnt signaling pathway plays an essential role for CD8 central memory T cell differentiation under physiological conditions in vivo. They raise the possibility that modulation of Wnt signaling may be exploited to improve the generation of CD8 memory T cells during vaccination or for therapies designed to promote sustained cytotoxic CD8 T cell responses against tumors.<\/jats:p>","DOI":"10.1073\/pnas.0914127107","type":"journal-article","created":{"date-parts":[[2010,5,11]],"date-time":"2010-05-11T00:20:03Z","timestamp":1273537203000},"page":"9777-9782","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":352,"title":["Essential role of the Wnt pathway effector Tcf-1 for the establishment of functional CD8 T cell memory"],"prefix":"10.1073","volume":"107","author":[{"given":"Gr\u00e9goire","family":"Jeannet","sequence":"first","affiliation":[{"name":"Ludwig Institute for Cancer Research Ltd., Lausanne Branch and University of Lausanne, 1066 Epalinges, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Boudousqui\u00e9","sequence":"additional","affiliation":[{"name":"Ludwig Institute for Cancer Research Ltd., Lausanne Branch and University of Lausanne, 1066 Epalinges, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"No\u00e9mie","family":"Gardiol","sequence":"additional","affiliation":[{"name":"Ludwig Institute for Cancer Research Ltd., Lausanne Branch and University of Lausanne, 1066 Epalinges, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joonsoo","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Graduate Program in Immunology and Virology, University of Massachusetts Medical School, Worcester, MA 01655; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joerg","family":"Huelsken","sequence":"additional","affiliation":[{"name":"Swiss Cancer Research Institute, Federal University of Technology Lausanne, 1015 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Werner","family":"Held","sequence":"additional","affiliation":[{"name":"Ludwig Institute for Cancer Research Ltd., Lausanne Branch and University of Lausanne, 1066 Epalinges, Switzerland;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,5,10]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2009.02.004"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2009.05.008"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.12.6833"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/87720"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.10.012"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.25.022106.141548"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.07.010"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20070841"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1403"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2009.05.014"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200636165"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01441"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1083317"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04790"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200637023"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2619"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1686208"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03319"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.3.1439"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/374070a0"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/90623"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.3.1777"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20071641"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-07-102558"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.1982"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901199"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1008"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-0934(91)90018-U"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0914127107","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T18:50:28Z","timestamp":1649789428000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0914127107"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,5,10]]},"references-count":28,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2010,5,25]]}},"alternative-id":["10.1073\/pnas.0914127107"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0914127107","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.3836972.3571080","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,5,10]]},"assertion":[{"value":"2010-05-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}