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However, factors, which influence the initiation and progression of an autoimmune response remain incompletely understood. By establishing a double\u2010transgenic BALB\/c mouse system in which different amounts of a cell\u2010surface neo\u2010self\u2010antigen are expressed under the CD11c promoter, we demonstrate that antigen dose dramatically influences T\u2010cell tolerance mechanisms. Moderate antigen expression in both hematopoietic and nonhematopoietic cells favors the development of antigen\u2010specific Treg cells and the establishment of a tolerogenic environment. In marked contrast, a high dose of antigen expression results in very stringent negative selection, in poor development of antigen\u2010specific Treg cells and in the early onset of anemia and splenomegaly and the late development of arthritis and high titers of IgG auto Abs. Disease is initiated by autoreactive T\u00a0cells, which escape negative selection by expressing a second TCR with a different specificity or an altered affinity. Transfer of Ag\u2010specific Treg cells ameliorates the early onset signs of disease but does not prevent the development of long\u2010term chronic pathologies. Altogether, our results suggest that Ag dose directly affects Treg\u2010cell generation and thus, the set\u2010up of T\u2010cell tolerance.<\/jats:p>","DOI":"10.1002\/eji.201343840","type":"journal-article","created":{"date-parts":[[2014,2,4]],"date-time":"2014-02-04T20:31:32Z","timestamp":1391545892000},"page":"1299-1312","source":"Crossref","is-referenced-by-count":7,"title":["The amount of self\u2010antigen determines the effector function of murine T\u00a0cells escaping negative selection"],"prefix":"10.1002","volume":"44","author":[{"given":"Lee K.","family":"Swee","sequence":"first","affiliation":[{"name":"Developmental and Molecular Immunology Department of Biomedicine University of Basel  Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anja","family":"Nusser","sequence":"additional","affiliation":[{"name":"Developmental and Molecular Immunology Department of Biomedicine University of Basel  Basel 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