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.
Associate Director, Division of Immunogenetics and Cellular Immunology
1. Xu Z, Ho S, Chang CC, Liu Z, Li M, Vasilescu, ER, Clynes RA, Vlad G, Suciu-Foca N. ILT3.FC inhibits the production of exosomes containing inflammatory microRNA in supernatants of alloactivated T cells. 2013 In press
2. Chen L, Xu Z, Chang CC, Ho S, Liu Z, Vlad G, Cortesini R, Clynes RA, Luo Y, Suciu-Foca N. Allospecific CD8 T suppressor cells induced by multiple MLC stimulation or priming in the presence of ILT3.Fc have similar gene expression profiles. Hum Immunol. 2013; doi:pii: S0198-8859(13)00563-6. 10.1016/j.humimm.2013.10.004.
3. Vlad G, Suciu-Foca N. Induction of Antigen-Specific Human T Suppressor Cells by Membrane and Soluble ILT3. Exp Mol Pathol. 2012; 93:294-301.
4. Chang CC, Zhang QY, Liu Z, Clynes RA, Suciu-Foca N, Vlad G. Downregulation of Inflammatory MicroRNAs by Ig-like Transcript 3 Is Essential for the Differentiation of Human CD8+ T Suppressor Cells. J Immunol. 2012 188:3042-3052
5. Vlad G, King J, Chang CC, Liu Z, Friedman RA, Torkamani AA, Suciu-Foca N. Gene profile analysis of CD8(+) ILT3-Fc induced T suppressor cells. Hum Immunol. 2011; 72:107-14.
6. Chang CC, Vlad G, D'Agati VD, Liu Z, Zhang QY, Witkowski P, Torkamani AA, Stokes MB, Ho EK, Cortesini R, Suciu-Foca N. BCL6 is required for differentiation of Ig-like transcript 3-Fc-induced CD8+ T suppressor cells. J Immunol. 2010; 185:5714-22.
Committees , Council, and Professional Society Memberships
American Society for Histocompatibility and Immunogenetics
T regulatory cells, immunological tolerance, transplantation