Genetic Engineering of T Cells for Immune Tolerance

Regulatory T cells (Tregs) play a role in the induction and maintenance of tolerance, as well as in modulating aberrant immune responses. While expanded Tregs have been used in clinical trials, they are polyclonal and the frequency of specific Tregs is very low. To overcome this issue, we have endeavored to "specify" Tregs by engineering them to express receptors that can recognize a given antigen and applied this protocol in autoimmunity, hemophilia and allergy. Thus, we have used retroviral transduction of a specific T cell receptor, single-chain variable fragments (Fvs), or antigen domains in Tregs to achieve this goal. This review summarizes our steps to achieve the ultimate goal of modulating human diseases.