{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T11:56:13Z","timestamp":1780401373345,"version":"3.54.1"},"reference-count":29,"publisher":"Rockefeller University Press","issue":"11","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2002,6,3]]},"abstract":"<jats:p>Regulation by transforming growth factor (TGF)-\u03b2 plays an important role in immune homeostasis. TGF-\u03b2 inhibits T cell functions by blocking both proliferation and differentiation. Here we show that TGF-\u03b2 blocks Th1 differentiation by inhibiting the expression of T-bet, the apparent masterregulator of T helper (Th)1 differentiation. Restoration of T-bet expression through retroviral transduction of T-bet into developing Th1 cells abrogated the inhibitory effect of TGF-\u03b2. In addition, we show that, contrary to prior suggestions, downregulation of interleukin 12 receptor \u03b22 chain is not key to the TGF-\u03b2\u2013mediated effect. Furthermore, we show that the direct inhibitory effect of TGF-\u03b2 on T cells is responsible, at least in part, for the inability of BALB\/c mice to mount a Leishmania-specific Th1 response and to clear Leishmanial infection.<\/jats:p>","DOI":"10.1084\/jem.20012076","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T16:48:54Z","timestamp":1027702134000},"page":"1499-1505","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":399,"title":["Mechanism of Transforming Growth Factor \u03b2\u2013induced Inhibition of T Helper Type 1 Differentiation"],"prefix":"10.1084","volume":"195","author":[{"given":"Leonid","family":"Gorelik","sequence":"first","affiliation":[{"name":"1Yale University School of Medicine, New Haven, CT 06520"},{"name":"2Howard Hughes Medical Institute, New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Constant","sequence":"additional","affiliation":[{"name":"1Yale University School of Medicine, New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard A.","family":"Flavell","sequence":"additional","affiliation":[{"name":"1Yale University School of Medicine, New Haven, CT 06520"},{"name":"2Howard Hughes Medical Institute, New Haven, CT 06520"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2002,5,28]]},"reference":[{"key":"2023072511171380500_BIB1","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1146\/annurev.immunol.16.1.137","volume":"16","year":"1998","journal-title":"Annu. Rev. Immunol."},{"key":"2023072511171380500_BIB2","doi-asserted-by":"crossref","first-page":"3514","DOI":"10.4049\/jimmunol.153.8.3514","volume":"153","year":"1994","journal-title":"J. Immunol."},{"key":"2023072511171380500_BIB3","doi-asserted-by":"crossref","first-page":"4773","DOI":"10.4049\/jimmunol.165.9.4773","volume":"165","year":"2000","journal-title":"J. Immunol."},{"key":"2023072511171380500_BIB4","doi-asserted-by":"crossref","first-page":"2639","DOI":"10.1002\/1521-4141(200009)30:9<2639::AID-IMMU2639>3.0.CO;2-7","volume":"30","year":"2000","journal-title":"Eur. J. Immunol."},{"key":"2023072511171380500_BIB5","doi-asserted-by":"crossref","first-page":"21597","DOI":"10.1074\/jbc.272.34.21597","volume":"272","year":"1997","journal-title":"J. Biol. Chem."},{"key":"2023072511171380500_BIB6","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/S0092-8674(00)80240-8","volume":"89","year":"1997","journal-title":"Cell."},{"key":"2023072511171380500_BIB7","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.4049\/jimmunol.161.4.1664","volume":"161","year":"1998","journal-title":"J. Immunol."},{"key":"2023072511171380500_BIB8","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S1074-7613(00)80170-3","volume":"12","year":"2000","journal-title":"Immunity."},{"key":"2023072511171380500_BIB9","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/S1074-7613(00)80343-X","volume":"6","year":"1997","journal-title":"Immunity."},{"key":"2023072511171380500_BIB10","first-page":"2289","volume":"12","year":"1998","journal-title":"J. Exp. Med."},{"key":"2023072511171380500_BIB11","doi-asserted-by":"crossref","first-page":"2671","DOI":"10.4049\/jimmunol.165.5.2671","volume":"165","year":"2000","journal-title":"J. Immunol."},{"key":"2023072511171380500_BIB12","doi-asserted-by":"crossref","first-page":"2861","DOI":"10.4049\/jimmunol.164.6.2861","volume":"164","year":"2000","journal-title":"J. Immunol."},{"key":"2023072511171380500_BIB13","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/S0092-8674(00)80702-3","volume":"100","year":"2000","journal-title":"Cell."},{"key":"2023072511171380500_BIB14","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1038\/382174a0","volume":"382","year":"1996","journal-title":"Nature."},{"key":"2023072511171380500_BIB15","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1126\/science.1059835","volume":"292","year":"2001","journal-title":"Science."},{"key":"2023072511171380500_BIB16","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1146\/annurev.iy.13.040195.001055","volume":"13","year":"1995","journal-title":"Annu. Rev. Immunol."},{"key":"2023072511171380500_BIB17","doi-asserted-by":"crossref","first-page":"6156","DOI":"10.4049\/jimmunol.161.11.6156","volume":"161","year":"1998","journal-title":"J. Immunol."},{"key":"2023072511171380500_BIB18","doi-asserted-by":"crossref","first-page":"3818","DOI":"10.1128\/IAI.66.8.3818-3824.1998","volume":"66","year":"1998","journal-title":"Infect. Immun."},{"key":"2023072511171380500_BIB19","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1084\/jem.185.5.817","volume":"185","year":"1997","journal-title":"J. Exp. Med."},{"key":"2023072511171380500_BIB20","doi-asserted-by":"crossref","first-page":"6776","DOI":"10.4049\/jimmunol.166.11.6776","volume":"166","year":"2001","journal-title":"J. Immunol."},{"key":"2023072511171380500_BIB21","doi-asserted-by":"crossref","first-page":"3442","DOI":"10.1073\/pnas.90.8.3442","volume":"90","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072511171380500_BIB22","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1126\/science.1636092","volume":"257","year":"1992","journal-title":"Science."},{"key":"2023072511171380500_BIB23","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1084\/jem.191.5.847","volume":"191","year":"2000","journal-title":"J. Exp. Med."},{"key":"2023072511171380500_BIB24","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/S1074-7613(00)80342-8","volume":"6","year":"1997","journal-title":"Immunity."},{"key":"2023072511171380500_BIB25","doi-asserted-by":"crossref","first-page":"3317","DOI":"10.4049\/jimmunol.158.7.3317","volume":"158","year":"1997","journal-title":"J. Immunol."},{"key":"2023072511171380500_BIB26","doi-asserted-by":"crossref","first-page":"4710","DOI":"10.1128\/iai.59.12.4710-4714.1991","volume":"59","year":"1991","journal-title":"Infect. Immun."},{"key":"2023072511171380500_BIB27","doi-asserted-by":"crossref","first-page":"6132","DOI":"10.4049\/jimmunol.162.10.6132","volume":"162","year":"1999","journal-title":"J. Immunol."},{"key":"2023072511171380500_BIB28","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.4049\/jimmunol.146.6.1849","volume":"146","year":"1991","journal-title":"J. Immunol."},{"key":"2023072511171380500_BIB29","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1006\/geno.2000.6361","volume":"70","year":"2000","journal-title":"Genomics."}],"container-title":["The Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/195\/11\/1499\/1704178\/jem195111499.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/195\/11\/1499\/1704178\/jem195111499.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T11:17:38Z","timestamp":1690283858000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/195\/11\/1499\/39416\/Mechanism-of-Transforming-Growth-Factor-induced"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,5,28]]},"references-count":29,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2002,6,3]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.20012076","relation":{},"ISSN":["1540-9538","0022-1007"],"issn-type":[{"value":"1540-9538","type":"electronic"},{"value":"0022-1007","type":"print"}],"subject":[],"published":{"date-parts":[[2002,5,28]]}}}