T cell tolerance in transplantation: possibilities for therapeutic intervention

It is now possible to induce donor-specific transplantation tolerance in adult rodents using a number of therapeutic strategies. These include the use of non-depleting monoclonal antibodies against T cell co-receptor and costimulation molecules, and immunisation with tolerogenic antigen-presenting cells. It is a common finding to all of these models of peripheral tolerance, as well as to various mouse models of autoimmune disease, that regulatory CD4(+) T cells are the principle mediators. There are currently no specific markers for regulatory T cells and their activity has been associated with different T cell subsets defined by the expression of activation markers, such as CD25 and cytotoxic T lymphocyte antigen-4 (CTLA-4), or anti-inflammatory cytokines, such as IL-10 and TGF-beta. Differential gene expression analyses have been used to identify potential new markers for regulatory T cells and to find novel targets for therapeutic manipulation of the immune system. The challenge now is to understand the biological principles that allow such immune reprogramming so that they can be safely applied to clinical situations.