Central Tolerance

Central tolerance is the mechanism by which newly developing T cells and B cells are rendered non-reactive to self. The concept of central tolerance was proposed in 1959 by Joshua Lederberg, as part of his general theory of immunity and tolerance, and is often mistakenly attributed to MacFarlane Burnet. Lederberg hypothesized that it is the age of the lymphocyte that defines whether an antigen that is encountered will induce tolerance, with immature lymphocytes being tolerance sensitive. Lederberg's theory that self-tolerance is 'learned' during lymphocyte development was a major conceptual contribution to immunology, and it was experimentally substantiated in the late 1980s when tools to analyze lymphocyte development became available. Central tolerance is distinct from periphery tolerance in that it occurs while cells are still present in the primary lymphoid organs (thymus and bone-marrow), prior to export into the periphery, while peripheral tolerance is generated after the cells reach the periphery. Regulatory T cells can be considered both central tolerance and peripheral tolerance mechanisms, as they can be generated from self(or foreign)-reactive T cells in the thymus during T cell differentiation, but they exert their immune suppression in the periphery on other self(or foreign)-reactive T cells.