Co-operative failure of Aire-mediated clonal deletion and Cblb-mediated clonal anergy in the pathogenesis of autoimmunity
Breakdown of self-tolerance in autoimmune diseases is poorly understood, as is the existence of so many different mechanisms for actively acquired tolerance. In this thesis, I find that failure of two tolerance mechanisms, thymic T cell clonal deletion to organ specific antigens mediated by Aire and the two-signal mechanisms of T cell tolerance in mature T cells imposed by the ubiquitin ligase Cblb, individually cause slow and subclinical autoimmunity but combine co-operatively to allow lethal...[Show more]
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