Maintenance of self-tolerance by apoptotic cell clearance.

ABSTRACT

Innate immune cells are genetically conferred the ability to recognize microorganisms as "non-self", and to induce appropriate immune responses to eliminate them. On the other hand, immune cells should recognize self cells in order to avoid attacking normal tissues. For this purpose, immune cells make use of self-cell corpses. When cells undergo apoptosis, cell corpses are rapidly phagocytosed by phagocytes, such as macrophages and dendritic cells. These phagocytes present self antigens derived from dead cell corpses to induce tolerance. Impairment of apoptotic cell clearance often results in autoimmune disorder. Intravenous injection of dead cell corpses can induce tolerance to cell-associated antigens, and this strategy has potential use in the treatment of various autoimmune and inflammatory disorders in human. Injected dead cell corpses are rapidly cleared by phagocytes located in the marginal zone (MZ) of spleen. Among those phagocytes, macrophages play a critical role in the rapid clearance of dead cell corpses, and the subsequent induction of tolerance to cell-associated antigens.