Central role of ILT3 in the T suppressor cell cascade.

CD8+ T suppressor cells differentiate both in vivo and in vitro upon chronic exposure of responding T cells to allogeneic APC. These Ts are allospecific and exhibit their function interacting directly with priming APC which they render tolerogenic. Tolerogenicity of professional and non-professional human APC, such as dendritic cells and endothelial cells, respectively is due to the upregulation of the inhibitory receptors ILT3 and ILT4. ILT3 signals both intracellularly, inhibiting NF-kappaB activation, and transcription of costimulatory molecules, and extracellularly, inducing anergy and regulatory function in T cells with cognate specificity. Both membrane and soluble ILT3 are proteins with potent immunosuppressive activity which are of importance for treatment of rejection, autoimmunity and cancer.