{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T15:49:13Z","timestamp":1791042553155,"version":"4.1.0"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2009,3,1]],"date-time":"2009-03-01T00:00:00Z","timestamp":1235865600000},"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":[[2009,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Mutant mice in which tyrosine 136 of linker for activation of T cells (LAT) was replaced with a phenylalanine (LatY136F mice) develop a lymphoproliferative disorder involving polyclonal CD4 effector T cells that produce massive amounts of IL-4 and trigger severe Th2 inflammation. Naive CD4 T cells can themselves produce IL-4 and thereby initiate a self-reinforcing positive regulatory loop that involves the STAT6 transcription factor and leads to Th2 polarization. We determined the functional outcome that results when LatY136F T cells differentiate in the absence of such STAT6-dependent regulatory loop. The lack of STAT6 had no effect on the timing and magnitude of the lymphoproliferative disorder. However, in LatY136F mice deprived of STAT6, the expanding CD4 T cell population was dominated by Th1 effector cells that triggered B cell proliferation, elevated IgG2a and IgG2b levels as well as the production of autoantibodies. In contrast to LatY136F mice that showed no CD8 T cell expansion, the CD8 T cells present in LatY136F mice deprived of STAT6 massively expanded and acquired effector potential. Therefore, the lack of STAT6 is sufficient to convert the Th2 lymphoproliferative disorder that characterizes LatY136F mice into a lymphoproliferative disorder that is dominated by Th1 and CD8 effector T cells. The possibility to dispose of a pair of mice that differs by a single gene and develops in the absence of deliberate immunization large numbers of Th cells with almost reciprocal polarization should facilitate the identification of genes involved in the control of normal and pathological Th cell differentiation.<\/jats:p>","DOI":"10.4049\/jimmunol.0803257","type":"journal-article","created":{"date-parts":[[2009,2,20]],"date-time":"2009-02-20T17:41:32Z","timestamp":1235151692000},"page":"2680-2689","source":"Crossref","is-referenced-by-count":22,"title":["STAT6 Deletion Converts the Th2 Inflammatory Pathology Afflicting\n                    <i>\n                      Lat\n                      <i>Y136F<\/i>\n                    <\/i>\n                    Mice into a Lymphoproliferative Disorder Involving Th1 and CD8 Effector T Cells"],"prefix":"10.1093","volume":"182","author":[{"given":"Cristel","family":"Archambaud","sequence":"first","affiliation":[{"name":"Centre d\u2019Immunologie de Marseille-Luminy, Universit\u00e9 de la M\u00e9diterran\u00e9e"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale , Unit\u00e9 631"},{"name":"Centre National de la Recherche Scientifique, Unit\u00e9 Mixte de Recherche 6102 , Marseille,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amandine","family":"Sansoni","sequence":"additional","affiliation":[{"name":"Centre d\u2019Immunologie de Marseille-Luminy, Universit\u00e9 de la M\u00e9diterran\u00e9e"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale , Unit\u00e9 631"},{"name":"Centre National de la Recherche Scientifique, Unit\u00e9 Mixte de Recherche 6102 , Marseille,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Mingueneau","sequence":"additional","affiliation":[{"name":"Centre d\u2019Immunologie de Marseille-Luminy, Universit\u00e9 de la M\u00e9diterran\u00e9e"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale , Unit\u00e9 631"},{"name":"Centre National de la Recherche Scientifique, Unit\u00e9 Mixte de Recherche 6102 , Marseille,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Devilard","sequence":"additional","affiliation":[{"name":"Centre d\u2019Immunologie de Marseille-Luminy, Universit\u00e9 de la M\u00e9diterran\u00e9e"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale , Unit\u00e9 631"},{"name":"Centre National de la Recherche Scientifique, Unit\u00e9 Mixte de Recherche 6102 , Marseille,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georges","family":"Delsol","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale Unit\u00e9 563"},{"name":"Universit\u00e9 Toulouse III Paul Sabatier"},{"name":"Centre Hospitalier de l\u2019Universit\u00e9 Purpan, Service d\u2019Anatomie Pathologique , Toulouse,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Malissen","sequence":"additional","affiliation":[{"name":"Centre d\u2019Immunologie de Marseille-Luminy, Universit\u00e9 de la M\u00e9diterran\u00e9e"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale , Unit\u00e9 631"},{"name":"Centre National de la Recherche Scientifique, Unit\u00e9 Mixte de Recherche 6102 , Marseille,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Malissen","sequence":"additional","affiliation":[{"name":"Centre d\u2019Immunologie de Marseille-Luminy, Universit\u00e9 de la M\u00e9diterran\u00e9e"},{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale , Unit\u00e9 631"},{"name":"Centre National de la Recherche Scientifique, Unit\u00e9 Mixte de Recherche 6102 , Marseille,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,3,1]]},"reference":[{"key":"2026012806361858900_R1","first-page":"616","article-title":"An epigenetic view of helper T cell differentiation.","volume-title":"Nat. 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