Membrane and soluble ILT3 are critical to the generation of T suppressor cells and induction of immunological tolerance.

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-kappaB 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.