T-cell vaccination for autoimmune diseases: immunologic lessons and clinical experience in multiple sclerosis.

Autoreactive T-cells are regulated under the normal conditions and play an important role in autoimmune pathologies when they are dysregulated as a result of genetic, environmental and other unknown factors associated with various autoimmune diseases. The immune regulation of autoreactive T-cells may be regained by activating the regulatory network, such as the idiotype anti-idiotypic network. Immunization with inactivated autoreactive T-cells (T-cell vaccination) can be used as a powerful means of activating the idiotype anti-idiotypic network to deplete specific subsets of autoreactive T-cells potentially involved in autoimmune conditions. 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. Recent clinical trials in multiple sclerosis have begun to reveal the role of T-cell vaccination in the understanding of in vivo regulation of autoreactive T-cells and in the development of effective therapeutic strategies for multiple sclerosis and other autoimmune conditions. In this article, we will review the recent advances in 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. Current issues and thoughts related to the preparation of T-cell vaccine, the relevant sources of autoimmune T-cells and epitope spreading are also discussed.