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.^[1] Peripheral tolerance can also serve a purpose in preventing an immune response to harmless food antigens and allergens.^[2]

Self reactive cells are subject to clonal deletion or clonal diversion. Both processes of peripheral tolerance control the presence and production of self reactive immune cells.^[3] 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.^[4] 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.^[5][4] Tregs, which are also generated during thymic T cell development, further suppress the effector functions of conventional lymphocytes in the periphery.^[6] 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.^[7]

Dependence of a particular antigen on either central or peripheral tolerance is determined by its abundance in the organism.^[8] B Cells have a lower probability that they will express cell surface markers to pose the threat of causing an autoimmune attack.^[9] Peripheral tolerance of B cells is largely mediated by B cell dependence on T cell help. However, B cell peripheral tolerance is much less studied.