{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:38:23Z","timestamp":1790141903095,"version":"4.0.1"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2012,5,1]],"date-time":"2012-05-01T00:00:00Z","timestamp":1335830400000},"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":[[2012,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>NK cell receptors (NKRs) such as NK1.1, NKG2D, and Ly49s are expressed on subsets of CD1d-independent memory phenotype CD8+ and CD4\u2013CD8\u2013 T cells. However, the mechanism for the generation and functions of these NKR+ T cells remained elusive. In this study, we found that CD1d-independent Ly49+ T cells were reduced severely in the spleen, bone marrow, and liver, but not thymus, in mice doubly deficient for IFN regulatory factor-2 (IRF-2) and CD1d, in which the overall memory phenotype T cell population was contrastingly enlarged. Because a large fraction of Ly49+ T cells coexpressed NK1.1 or NKG2D, the reduction of Ly49+ T cells resulted indirectly in underrepresentation of NK1.1+ or NKG2D+ cells. Ly49+ T cell deficiency was observed in IRF-2\u2212\/\u2212 mice additionally lacking IFN-\u03b1\/\u03b2R \u03b1-chain (IFNAR1) as severely as in IRF-2\u2212\/\u2212 mice, arguing against the involvement of the accelerated IFN-\u03b1\/\u03b2 signals due to IRF-2 deficiency. Rather, mice lacking IFN-\u03b1\/\u03b2R alone also exhibited relatively milder Ly49+ T cell reduction, and IL-2 could expand Ly49+ T cells from IFNAR1\u2212\/\u2212, but not from IRF-2\u2212\/\u2212, spleen cells in vitro. These results together indicated that IRF-2 acted in Ly49+ T cell development in a manner distinct from that of IFN-\u03b1\/\u03b2 signals. The influence of IRF-2 deficiency on Ly49+ memory phenotype T cells observed in this study suggested a unique transcriptional program for this T cell population among other NKR+ T and memory phenotype T cells.<\/jats:p>","DOI":"10.4049\/jimmunol.1200210","type":"journal-article","created":{"date-parts":[[2012,4,14]],"date-time":"2012-04-14T05:00:21Z","timestamp":1334379621000},"page":"4838-4845","source":"Crossref","is-referenced-by-count":8,"title":["Differential Requirements for IRF-2 in Generation of CD1d-Independent T Cells Bearing NK Cell Receptors"],"prefix":"10.1093","volume":"188","author":[{"given":"Tsuyoshi","family":"Notake","sequence":"first","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Shinshu University Graduate School of Medicine , Matsumoto 390-8621 ,","place":["Japan"]},{"name":"Department of Surgery, Shinshu University School of Medicine , Matsumoto 390-8621 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin","family":"Horisawa","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Shinshu University Graduate School of Medicine , Matsumoto 390-8621 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideki","family":"Sanjo","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Shinshu University Graduate School of Medicine , Matsumoto 390-8621 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shin-ichi","family":"Miyagawa","sequence":"additional","affiliation":[{"name":"Department of Surgery, Shinshu University School of Medicine , Matsumoto 390-8621 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeaki","family":"Hida","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Shinshu University Graduate School of Medicine , Matsumoto 390-8621 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinsuke","family":"Taki","sequence":"additional","affiliation":[{"name":"Department of Immunology and Infectious Diseases, Shinshu University Graduate School of Medicine , Matsumoto 390-8621 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2012,5,15]]},"reference":[{"key":"2025032410084453500_r1","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/S0952-7915(00)00242-9","article-title":"Expression and function of NK cell receptors in CD8+ T cells","volume":"13","author":"McMahon","year":"2001","journal-title":"Curr. 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Induction of Stat-1 and IFN consensus sequence binding protein expression by T cell activation","volume":"156","author":"Nelson","year":"1996","journal-title":"J. Immunol."},{"key":"2025032410084453500_r34","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1084\/jem.20020772","article-title":"Interleukin 15 controls both proliferation and survival of a subset of memory-phenotype CD8(+) T cells","volume":"196","author":"Judge","year":"2002","journal-title":"J. Exp. 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