Peripheral tolerance

In immunology, peripheral tolerance is the second branch of immunological tolerance, after central tolerance. It takes place in the immune periphery (after T and B cells egress from primary lymphoid organs). Its main purpose is to ensure that self-reactive T and B cells which escaped central tolerance do not cause autoimmune disease. Peripheral tolerance prevents immune response to harmless food antigens and allergens, too.

Deletion of self-reactive T cells in the thymus is only 60-70% efficient, and naive T cell repertoire contains a significant portion of low-avidity self-reactive T cells. These cells can trigger an autoimmune response, and there are several mechanisms of peripheral tolerance to prevent their activation. Antigen-specific mechanisms of peripheral tolerance include persistent of T cell in quiescence, ignorance of antigen and direct inactivation of effector T cells by either clonal deletion, conversion to regulatory T cells (Tregs) or induction of anergy. Tregs, which are also generated during thymic T cell development, further suppress the effector functions of conventional lymphocytes in the periphery. Dendritic cells (DCs) participate in the negative selection of autoreactive T cells in the thymus, but they also mediate peripheral immune tolerance through several mechanisms.

Dependence of a particular antigen on either central or peripheral tolerance is determined by its abundance in the organism. B cell peripheral tolerance is much less studied and is largely mediated by B cell dependence on T cell help.