Determinant spreading during experimental autoimmune encephalomyelitis: is it potentiating, protecting or...

During many autoimmune conditions, a T-cell response initially focused to a self-antigen evolves towards the recruitment of T cells to multiple antigenic determinants. Here we discuss whether such determinant spreading involves T cells activated in the peripheral lymphoid organs, or alternatively, whether the diversification occurs after infiltration of the initiating T cells into the target organ, for example, into the central nervous system during experimental autoimmune encephalomyelitis, a prototype for multiple sclerosis. The expression of myelin antigens in the thymus and spleen may not only contribute to the induction of tolerance but also to determinant spreading. In this case, the outcome of in vivo diversification may ultimately be determined by the balance between type 1 and type 2 responses to antigenic determinants derived from myelin components. Thus, spreading T cells could modulate disease progression positively or negatively, depending upon the nature of the accompanying cytokine secretion profile.