Similar to helper and cytotoxic T cells, CD8(+) T suppressor cells (Ts) acquire antigen specificity via direct interaction with antigen-presenting cells (APC). They induce the upregulation of the inhibitory receptor immunoglobulin-like transcript (ILT)3 on professional and nonprofessional APC, rendering these cells tolerogenic and able to induce the differentiation of further waves of regulatory and suppressor T cells. This review sums up evidence that ILT3 is the centerpiece of CD8(+) Ts-driven suppression and acts as a master switch in the regulation of CD8(+) and CD4(+) T-cell responses to antigens in transplantation, autoimmunity, allergy, and cancer.