As pathogenic autoreactive T cells are viewed as pathogens in T cell-mediated autoimmune conditions, they can be used, when rendered attenuated by irradiation or chemical treatment, as vaccine to activate regulatory immune responses of the host against circulating autoreactive T cells [1]. Immunization with inactivated autoreactive T cells (T cell vaccination) selected from individual’s own T cell repertoire provides a unique in vivo setting for testing immune regulation that is known to involve interactions of a variety of related surface molecules (e.g. T cell receptors) and secreted molecules (e.g. cytokines). It induces regulatory immune responses that closely resemble the in vivo situation where the immune system is challenged by clonal activation and expansion of given T cell populations in various autoimmune diseases. By the same token, T cell vaccination provides a powerful means of eliciting natural reactions of the immune system in response to clonal expansion of T cells, which can used as a therapeutic approach to suppress or eliminate specific pathogenic autoreactive T cells in autoimmune conditions. Clinical trials using T cell vaccination to deplete autoreactive T cells in human autoimmune conditions have begun to reveal the pathologic relevance of various autoimmune T cell populations in the disease processes, providing a unique opportunity to test the autoimmune theories in a clinical setting. The purpose of this article is to review the most recent advances in the area of T cell vaccination in relationship to the regulatory mechanism induced by T cell vaccination and the potential of T cell vaccination as a treatment for T cell-mediated autoimmune diseases, taking multiple sclerosis as an example. A significant portion of the discussion is devoted to the possibilities of improving the specificity and potency of T cell vaccine in multiple sclerosis.