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To determine whether the accumulation of activated T cells in CTLA\u20104<jats:sup>\u2212\/\u2212<\/jats:sup> mice is due to a defect in thymic selection, we examined negative selection in CTLA\u20104<jats:sup>\u2212\/\u2212<\/jats:sup> mice using two transgenic T cell receptor (TCR) models of thymic selection. Neither the H\u2010Y\u2010specific TCR nor the lymphocytic choriomeningitis virus (LCMV)\u2010specific TCR transgenic models revealed a defect in positive or negative selection in CTLA\u20104<jats:sup>\u2212\/\u2212<\/jats:sup> mice <jats:italic>in vivo<\/jats:italic> or <jats:italic>in vitro.<\/jats:italic> In fact, the negatively selecting phenotype of male H\u2010YTCR\u2010transgenic mice greatly mitigated the accumulation of activated peripheral T cells. Further, peripheral CTLA\u20104<jats:sup>\u2212\/\u2212<\/jats:sup> T cells expressing a single LMCV\u2010specific transgenic TCR did not have an activated phenotype, indicating that CTLA\u20104<jats:sup>\u2212\/\u2212<\/jats:sup> T cells require specific antigen for proliferation. These results demonstrate that specific antigen is required for the lymphoproliferation observed in CTLA\u20104<jats:sup>\u2212\/\u2212<\/jats:sup> mice, and that CTLA\u20104 deficiency does not lead to a gross defect in negative selection.<\/jats:p>","DOI":"10.1002\/eji.1830270811","type":"journal-article","created":{"date-parts":[[2007,3,2]],"date-time":"2007-03-02T05:38:11Z","timestamp":1172813891000},"page":"1887-1892","source":"Crossref","is-referenced-by-count":45,"title":["Normal thymic selection, normal viability and decreased lymphoproliferation in T cell receptor\u2010transgenic CTLA\u20104\u2010deficient mice"],"prefix":"10.1002","volume":"27","author":[{"given":"Paul","family":"Waterhouse","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin F.","family":"Bachmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josef M.","family":"Penninger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela S.","family":"Ohashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tak W.","family":"Mak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,12,7]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.iy.07.040189.002305"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-5699(94)90080-9"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.182.2.459"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(94)90071-X"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.3.811"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.270.5238.985"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(95)90125-6"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.6.2533"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.6.2541"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5265.1170"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.1996.tb00925.x"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-9822(02)00506-7"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.184.5.1631"},{"key":"e_1_2_1_15_2","doi-asserted-by":"crossref","first-page":"2453","DOI":"10.4049\/jimmunol.151.5.2453","volume":"151","author":"Nelson A. 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