The immune system is made of effecter and regulatory cells. The effecter cells such as T and B-lymphocytes function as soldiers fighting against infection through a process known as immunity while regulatory cells such as antigen presenting cells (APC) as commanders. The APC initiate immunity by capturing and presenting antigen to effecter cells. Since both foreign and self-antigens might be presented by the APCs, mechanisms are required to prevent the immune system from fighting against self: autoimmunity. While it is known that T and B cells undergo negative selection during development, which eliminates or inactivates self-reactive lymphocytes, the negative selection, however, appears far from complete since self-reactive lymphocyte can be readily identified in the immune repertoire; and these lymphocytes can cause fulminate autoimmune diseases under various circumstances.
The mechanisms that keep self-reactive lymphocytes “under check” are incompletely understood. Findings from our recent studies suggest that APCs regulate their antigen-presentation function during development in such a way that they preferentially present self-antigen at immature stages but foreign antigens at mature stages. A highly conserved protein, HLA-DO participates in this regulation. We propose that the developmentally regulated antigen presentation plays an important role in the induction of self-tolerance, a non-responsive state towards self-antigens, and that such tolerance induction occurs in the peripheral lymphoid tissue and bone marrow, involving inactivation of self-reactive lymphocytes as well as generation of suppressive FoxP3+ regulatory T cells. We are actively investigating towards this direction. A clear understanding of these mechanisms will not only impact the basic immunology but also bring in novel therapeutic management in autoimmune diseases and organ rejection in transplantation medicine.