{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T04:24:32Z","timestamp":1760502272496,"version":"3.38.0"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2020,5,1]],"date-time":"2020-05-01T00:00:00Z","timestamp":1588291200000},"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":[[2020,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>TCR signaling is required for homeostasis of naive \u03b1\u03b2 T cells. However, whether such a signal is necessary for \u03b3\u03b4 T cell homeostasis in the periphery remains unknown. In this study, we present evidence that a portion of V\u03b32+ \u03b3\u03b4 T cells, one of the major \u03b3\u03b4 T cell subsets in the secondary lymphoid organs, requires TCR signaling for homeostasis. To attenuate \u03b3\u03b4TCR signals, we generated mice lacking E\u03b34 (E\u03b34\u2212\/\u2212), an enhancer located at the 3\u2032-most end of the TCR\u03b3 locus. Overall, we found that in thymus, E\u03b34 loss altered V-J rearrangement, chromatin accessibility, and transcription of the TCR\u03b3 locus in a distance-dependent manner. V\u03b32+ \u03b3\u03b4 T cells in E\u03b34\u2212\/\u2212 mice developed normally both fetal and adult mouse thymi but were relatively reduced in number in spleen and lymph nodes. Although V\u03b32 TCR transcription decreased in all subpopulations of E\u03b34\u2212\/\u2212 mice, the number of V\u03b32+ \u03b3\u03b4 T cells decreased and TCR signaling was attenuated only in the innate-like CD27+CD45RBhigh subpopulation in peripheral lymphoid organs. Consistently, CD27+CD45RBhigh V\u03b32+ \u03b3\u03b4 T cells from E\u03b34\u2212\/\u2212 mice transferred into Rag2-deficient mice were not efficiently recovered, suggesting that continuous TCR signaling is required for their homeostasis. Finally, CD27+CD45RBhigh V\u03b32+ \u03b3\u03b4 T cells from E\u03b34\u2212\/\u2212 mice showed impaired TCR-induced activation and antitumor responses. These results suggest that normal homeostasis of innate-like CD27+CD45RBhigh V\u03b32+ \u03b3\u03b4 T cells in peripheral lymphoid organs requires TCR signaling.<\/jats:p>","DOI":"10.4049\/jimmunol.1801243","type":"journal-article","created":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T20:25:18Z","timestamp":1585772718000},"page":"2671-2684","source":"Crossref","is-referenced-by-count":5,"title":["Innate-like CD27+CD45RBhigh \u03b3\u03b4 T Cells Require TCR Signaling for Homeostasis in Peripheral Lymphoid Organs"],"prefix":"10.1093","volume":"204","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2388-776X","authenticated-orcid":false,"given":"Shizue","family":"Tani-ichi","sequence":"first","affiliation":[{"name":"Laboratory of Biological Chemistry, Human Health Sciences, Graduate School of Medicine, Kyoto University , Kyoto 606-8507 ,","place":["Japan"]},{"name":"Laboratory of Immune Regulation, Department of Virus Research, Institute for Frontier Life and Medical Sciences, Kyoto University , Kyoto 606-8507 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keisuke","family":"Wagatsuma","sequence":"additional","affiliation":[{"name":"Laboratory of Immune Regulation, Department of Virus Research, Institute for Frontier Life and Medical Sciences, Kyoto University , Kyoto 606-8507 ,","place":["Japan"]},{"name":"Graduate School of Medicine, Kyoto University , Kyoto 606-8501 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3845-8434","authenticated-orcid":false,"given":"Takahiro","family":"Hara","sequence":"additional","affiliation":[{"name":"Laboratory of Immune Regulation, Department of Virus Research, Institute for Frontier Life and Medical Sciences, Kyoto University , Kyoto 606-8507 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangwei","family":"Cui","sequence":"additional","affiliation":[{"name":"Laboratory of Immune Regulation, Department of Virus Research, Institute for Frontier Life and Medical Sciences, Kyoto University , Kyoto 606-8507 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinya","family":"Abe","sequence":"additional","affiliation":[{"name":"Laboratory of Immune Regulation, Department of Virus Research, Institute for Frontier Life and Medical Sciences, Kyoto University , Kyoto 606-8507 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hitoshi","family":"Miyachi","sequence":"additional","affiliation":[{"name":"Reproductive Engineering Team, Institute for Frontier Life and Medical Sciences, Kyoto University , Kyoto 606-8507 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satsuki","family":"Kitano","sequence":"additional","affiliation":[{"name":"Reproductive Engineering Team, Institute for Frontier Life and Medical Sciences, Kyoto University , Kyoto 606-8507 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koichi","family":"Ikuta","sequence":"additional","affiliation":[{"name":"Laboratory of Immune Regulation, Department of Virus Research, Institute for Frontier Life and Medical Sciences, Kyoto University , Kyoto 606-8507 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,5,15]]},"reference":[{"key":"2025030417511812500_r1","doi-asserted-by":"crossref","first-page":"2204","DOI":"10.1073\/pnas.88.6.2204","article-title":"Identification of a T-cell-specific enhancer at the locus encoding T-cell antigen receptor \u03b3 chain","volume":"88","author":"Kappes","year":"1991","journal-title":"Proc. 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