{"id":413,"date":"2013-06-04T19:23:59","date_gmt":"2013-06-04T10:23:59","guid":{"rendered":"http:\/\/exp.immunol.ifrec.osaka-u.ac.jp\/?p=413"},"modified":"2013-08-26T10:40:34","modified_gmt":"2013-08-26T01:40:34","slug":"%e5%b1%b1%e5%8f%a3%e5%87%86%e6%95%99%e6%8e%88%e3%81%ae%e5%88%b6%e5%be%a1%e6%80%a7t%e7%b4%b0%e8%83%9e%e3%81%ab%e3%81%8a%e3%81%91%e3%82%8bil2%e6%8a%91%e5%88%b6%e3%81%a8ctla4%e3%81%ae%e7%99%ba%e7%8f%be","status":"publish","type":"post","link":"http:\/\/exp.immunol.ifrec.osaka-u.ac.jp\/?p=413","title":{"rendered":"\u5c71\u53e3\u51c6\u6559\u6388\u306e\u5236\u5fa1\u6027T\u7d30\u80de\u306b\u304a\u3051\u308bIl2\u6291\u5236\u3068CTLA4\u306e\u767a\u73fe\u306e\u91cd\u8981\u6027\u306b\u3064\u3044\u3066\u306e\u8ad6\u6587\u304c PNAS\u306b\u63b2\u8f09"},"content":{"rendered":"<p>\u5c71\u53e3\u51c6\u6559\u6388\u306e\u5236\u5fa1\u6027T\u7d30\u80de\u306b\u304a\u3051\u308bIl2\u6291\u5236\u3068CTLA4\u306e\u767a\u73fe\u306e\u91cd\u8981\u6027\u306b\u3064\u3044\u3066\u306e\u8ad6\u6587\u304c PNAS\u306b\u63b2\u8f09\u3055\u308c\u307e\u3057\u305f\u3002<\/p>\n<p>Yamaguchi.T et al. Construction of self-recognizing regulatory T cells from conventional T cells by controlling CTLA-4 and IL-2 expression. Proc Natl Acad Sci U S A 110, E2116-2125 (2013).<\/p>\n<p>&nbsp;<\/p>\n<p><img loading=\"lazy\" decoding=\"async\" style=\"display: block; margin-left: auto; margin-right: auto;\" title=\"yamaguchi_pnas.jpg\" src=\"http:\/\/exp.immunol.ifrec.osaka-u.ac.jp\/wp-content\/uploads\/2013\/08\/yamaguchi_pnas.jpg\" border=\"0\" alt=\"Yamaguchi pnas\" width=\"467\" height=\"600\" \/><\/p>\n<p>Abstract:<\/p>\n<p>Thymus-produced CD4(+) regulatory T (Treg) cells, which specifically express the transcription factor forkhead box p3, are potently immunosuppressive and characteristically possess a self-reactive T-cell receptor (TCR) repertoire. To determine the molecular basis of Treg suppressive activity and their self-skewed TCR repertoire formation, we attempted to reconstruct these Treg-specific properties in conventional T (Tconv) cells by genetic manipulation. We show that Tconv cells rendered IL-2 deficient and constitutively expressing transgenic cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) were potently suppressive in vitro when they were preactivated by antigenic stimulation. They also suppressed in vivo inflammatory bowel disease and systemic autoimmunity\/inflammation produced by Treg deficiency. In addition, in the thymus, transgenic CTLA-4 expression in developing Tconv cells skewed their TCR repertoire toward higher self-reactivity, whereas CTLA-4 deficiency specifically in developing thymic Treg cells cancelled their physiological TCR self-skewing. The extracellular portion of CTLA-4 was sufficient for the suppression and repertoire shifting. It interfered with CD28 signaling to responder Tconv cells via outcompeting CD28 for binding to CD80 and CD86,or modulating CD80\/CD86 expression on antigen-presenting cells. Thus, a triad of IL-2 repression, CTLA-4 expression, and antigenic stimulation is a minimalistic requirement for conferring Treg-like suppressive activity on Tconv cells, in accordance with the function of forkhead box p3 to strongly repress IL-2 and maintain CTLA-4 expression in natural Treg cells. Moreover, CTLA-4 expression is a key element for the formation of a self-reactive TCR repertoire in natural Treg cells. These findings can be exploited to control immune responses by targeting IL-2 and CTLA-4 in Treg and Tconv cells.<\/p>","protected":false},"excerpt":{"rendered":"<p>\u5c71\u53e3\u51c6\u6559\u6388\u306e\u5236\u5fa1\u6027T\u7d30\u80de\u306b\u304a\u3051\u308bIl2\u6291\u5236\u3068CTLA4\u306e\u767a\u73fe\u306e\u91cd\u8981\u6027\u306b\u3064\u3044\u3066\u306e\u8ad6\u6587\u304c PNAS\u306b\u63b2\u8f09\u3055\u308c\u307e\u3057\u305f\u3002 Yamaguchi.T et al. Construction of self-recognizing r [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3,5,10],"tags":[],"_links":{"self":[{"href":"http:\/\/exp.immunol.ifrec.osaka-u.ac.jp\/index.php?rest_route=\/wp\/v2\/posts\/413"}],"collection":[{"href":"http:\/\/exp.immunol.ifrec.osaka-u.ac.jp\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"http:\/\/exp.immunol.ifrec.osaka-u.ac.jp\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"http:\/\/exp.immunol.ifrec.osaka-u.ac.jp\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"http:\/\/exp.immunol.ifrec.osaka-u.ac.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=413"}],"version-history":[{"count":7,"href":"http:\/\/exp.immunol.ifrec.osaka-u.ac.jp\/index.php?rest_route=\/wp\/v2\/posts\/413\/revisions"}],"predecessor-version":[{"id":464,"href":"http:\/\/exp.immunol.ifrec.osaka-u.ac.jp\/index.php?rest_route=\/wp\/v2\/posts\/413\/revisions\/464"}],"wp:attachment":[{"href":"http:\/\/exp.immunol.ifrec.osaka-u.ac.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=413"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"http:\/\/exp.immunol.ifrec.osaka-u.ac.jp\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=413"},{"taxonomy":"post_tag","embeddable":true,"href":"http:\/\/exp.immunol.ifrec.osaka-u.ac.jp\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=413"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}