Apoptosis: the quiet death silences the immune system.

Apoptosis plays an essential role in maintaining cellular homeostasis during development, differentiation, and pathophysiological processes. In the immune system, recent investigations reveal that during the course of T-cell development in the thymus, negative selection of autoreactive immature T-cells is a typical apoptotic process. In addition, apoptosis is also involved in cytotoxic killing of target cells and the regulation of lymphocyte homeostasis during immune responses. Interestingly, recent evidence has suggested that cells dying by apoptosis are actively involved in immunosuppression in various circumstances. We have shown that apoptotic cells could inhibit the expression of CD69 during T-cell activation. Furthermore, apoptotic cells phagocytosed by macrophages and/or dendritic cells are immunosuppressive, a process likely mediated by the production of transforming growth factor-beta1. Since apoptosis is a common mechanism by which excessive cells in many tissues and organs are eliminated in various pathophysiological processes, we believe that further investigation into the mechanisms by which apoptotic cells affect the immune system will not only lead to a better understanding of the significance of apoptosis during immune responses, but will also provide novel strategies for the management of autoimmune diseases and transplantation.