Tolerance, Autoimmunity and Immunopathology

Abstract

Many viral infections are efficiently defeated by a vigorousy cytotoxic T cell mediated early immune response. Before T cells in the periphery can be activated they have to undergo thymic positive and negative selection. During positive selection T cells acquire the capacity to H-2 restrictedly recognize the foreign antigens whereas negative selection prevents the development of self reactive T cells. However not all self antigens are presented to the developing T cells in the thymus to establish the so called central tolerance by physical elimination of self reactive T cells (Kappler et al. 1988; MacDonald et al. 1988). Therefore potentially autoreactive T cells may reach the periphery. These cells are presumable involved in many autoimmune disease processes (Sinha et al. 1990; Zamvil and Steinman, 1990). Several studies have shown that potentially self reactive T cells may be rendered tolerant to self antigens not expressed in the thymus by extrathymic mechanisms of tolerance induction (Webb and Sprent, 1990; Hanahan et al. 1990; Ramsdell and Fowlkes, 1990; Schönrich et al. 1991; Schoenrich et al. 1992).