Regulatory T-cell subsets and their roles in transplantation tolerance

PURPOSE OF REVIEW: Accumulating evidence indicates that regulatory T cells play a critical role in regulating various immune responses. This review summarizes the current literature regarding the roles and mechanisms of regulatory T-cell subsets in transplantation tolerance. RECENT FINDINGS: Numerous studies suggest that regulatory T cells can be induced by transplant tolerance protocols, and regulatory T cells are required for both induction and maintenance of transplantation tolerance. In addition, advances have been made in understanding the thymic versus extrathymic development of regulatory T cells, the location and timing of regulatory T-cell-mediated suppression, as well as the cell surface molecules and cytokines that are involved in modulating regulatory T-cell activity. The antigen specificity and molecular mechanisms by which regulatory T cells exert their function, however, remain controversial. Attention has also been focused on the therapeutic use of regulatory T cells in preventing allograft rejection either by in-vitro generation of large-scale functional regulatory T cells or by in-vivo induction and expansion of regulatory T cells. SUMMARY: Further understanding the molecular mechanisms that are important for activation and function of regulatory T-cell subsets may lead to the development of novel therapies for the induction and maintenance of donor-specific transplantation tolerance.