Regulatory T cells

Abstract

Cellular therapy employing Foxp3-expressing regulatory T cells (Tregs) holds the promise to replace and/or supplement indiscriminatory immunosuppression by drugs. In order to achieve this goal in the clinic we need to learn more about the generation, lifestyle, and function of Tregs. One way to generate Tregs of any desired antigen specificity is the retroviral introduction of the Foxp3 gene into activated CD4 T cells. Foxp3 is mostly but not exclusively a transcriptional repressor that interferes with T-cell receptor (TCR)-dependent activation of genes and may exert its effect, at least in part, by compromising NF-AT-dependent gene activation. Another way of generating Tregs extrathymically in vivo is the introduction of low amounts of peptides under subimmunogenic conditions. Such artificially induced Tregs have a long lifespan in the absence of the inducing antigen and can thus mediate antigen-specific tolerance. Antigen specificity of Tregs-mediated immunosuppression is due to effective co-recruitment and expression of Tregs and T effector cells to antigen-draining lymph nodes and sites of inflammation such that Tregs effectively suppress neighboring effector T cells at early or late stages of their differentiation. The latter allows for interference with already established unwanted immunity and may thus be employed to treat rather than prevent unwanted immune reactions.