The tolerogenic phenotype of human dendritic cells is characterized by high cell surface expression of the inhibitory receptor ILT3. ILT3 signals both intracellularly inhibiting tyrosine phosphorylation, NF-κB and MAPK p38 activity, transcription of certain co-stimulatory molecules, secretion of cytokines and chemokines, and extracellularly into the T cells with which the dendritic cells interact. Both ILT3^high tolerogenic dendritic cells and soluble ILT3 induce CD4 Th anergy and differentiation of antigen specific CD8 T suppressor cells. Recombinant ILT3-Fc protein has important immunotherapeutic potential acting directly on activated T cells and promoting the induction of immunological tolerance.