George Vlad, PhD

Our laboratory has focused on the induction of antigen-specific immunological tolerance based on the immune system’s own self restricting mechanisms. Using molecular and cellular immunology techniques, we established that the inhibitory receptors ILT3 and ILT4 are crucial to the tolerogenic phenotype acquired by professional and non-professional antigen presenting cells. The over expression of ILT3 on APC induces the differentiation of antigen-specific CD8 T suppressor cells during priming. In the context of transplantation, the bi-directional interaction between APC and T suppressor cells triggers a cascade of events which results in graft adaptation and T cell unresponsiveness to alloantigens presented via the direct and indirect pathways. We engineered a recombinant ILT3-Fc protein and demonstrated that, without any complementary iatrogenic immunosuppression, it inhibits xenospecific GVHD and induces allogeneic tolerance to human pancreatic islets in humanized NOD/SCID mouse models. ILT3-Fc induces a particular gene expression signature in primed CD8 T cells, which we have demonstrated to be characteristic of T suppressor cells. The up-regulation of genes with immunoregulatory function is concurrent with the down-regulation of several proinflammatory miRNA. Our studies currently focus on the potential of ILT3-Fc as an immunosuppressive agent in transplantation and autoimmune diseases.