Immunoglobulin-like transcript 3 (ILT3) and ILT4 belong to a family of inhibitory receptors expressed by human monocytes and dendritic cells. We show here that CD8+CD28− alloantigen-specific T suppressor (Ts) cells induce the up-regulation of ILT3 and ILT4 on monocytes and dendritic cells, rendering these antigen-presenting cells (APCs) tolerogenic. Tolerogenic APCs show reduced expression of costimulatory molecules and induce antigen-specific unresponsiveness in CD4+T helper cells. Studies of human heart transplant recipients showed that rejection-free patients have circulating Ts cells, which induce the up-regulation of ILT3 and ILT4 in donor APCs. These findings demonstrate an important mechanism of immune regulation.