Dr. Alegre’s research focuses on the inhibition of immune responses for the prevention of autoimmunity and transplant rejection in experimental mouse models. This research program comprises 2 main areas: the molecular, biochemical and functional properties of T cell inhibitory receptors, such as CTLA-4 and PD-1 in vitro and in vivo; the signaling pathways contributing to the development of an autoimmune or alloimmune response in vivo. Her laboratory has shown that engagement of CTLA-4 in T cells resulted in inhibition of the transcription factor NF-kappaB in vitro and could result in prevention of lymphoproliferative disease, hemolytic anemia and transplant rejection. More recent work has identified T cell-NF-kappaB as essential for the rejection of cardiac but not skin allografts and current work addresses potential differences between transplanted organs as well as mechanisms by which NF-kappaB-impaired T cells can undergo successful activation. These questions have led to the discovery that TLR signals, engaged in organs colonized by commensal bacteria, are necessary and sufficient to prevent the induction of transplantation tolerance in vivo.