Antigen-induced regulatory T cells in autoimmunity

It is possible that antigen-specific regulatory T (TReg) cells can be induced to prevent or treat autoimmune diseases. The effector functions of antigen-induced TReg cells cannot be defined uniformly and have to be analysed in relation to the disease process that they suppress. So far, TReg cells can only be classified and detected according to their in vivo regulatory effector functions, such as cytokine production, and not by the expression of specific cell-surface markers. Bystander suppression mediated by interleukin-4 (IL-4) and IL-10 (and possibly other cytokines) that can lead to the modulation of antigen-presenting cell function seems to be the main effector mechanism of antigen-induced TReg cells for suppressing autoaggressive T cells in vivo. Although clinical applications of TReg cells are feasible, conditions for their induction need to be better defined, in part to avoid the concomitant augmentation of autoaggressive T cells. The ability to track TReg cells in peripheral blood will be essential. Both mucosal and systemic routes of immunization can induce TReg cells. Antigen-induced TReg cells might contribute to the homeostatic balance of the immune system. Antigen-induced TReg cells escape thymic negative selection and recognize autoantigens, but they proliferate poorly compared with autoaggressive effector T cells. Antigen-induced TReg cells do not necessarily express CD25 and are, therefore, distinct from CD4+CD25+ 'naturally occurring' TReg cells. The use of immunodeficient hosts to 'read-out' TReg-cell function in vivo makes it difficult to distinguish between active regulatory function and homeostatic effects.