Cross talk between human regulatory T cells and antigen-presenting cells: Lessons for clinical applications.
Regulatory T cells (Tregs) have a critical role in maintaining self-tolerance and immune homeostasis. There is much interest in using Tregs as a cell therapy to re-establish tolerance in conditions such as inflammatory bowel disease and type 1 diabetes, with many ongoing clinical studies testing the safety and efficacy of this approach. Manufacturing of Tregs for therapy typically involves ex vivo expansion to obtain sufficient cell numbers for infusion and comes with the risk of altering the activity of key biological processes. However, this process also offers an opportunity to tailor Treg function to maximize in vivo activity. In this review, we focus on the roles of antigen-presenting cells (APCs) in the generation and function of Tregs in humans. In addition to stimulating the development of Tregs, APCs activate Tregs and provide signals that induce specialized functional and homing marker expression. Cross talk between Tregs and APCs is a critical, often under-appreciated, aspect of Treg biology, with APCs mediating the key properties of infectious tolerance and bystander suppression. Understanding the biology of human Treg-APC interactions will reveal new ways to optimize Treg-based therapeutic approaches.
['Wardell|Christine M|CM|0000-0002-2418-5076', 'MacDonald|Katherine N|KN|0000-0003-4883-2757', 'Levings|Megan K|MK|0000-0002-0305-5790', 'Cook|Laura|L|0000-0003-3153-2045']
D000938:Antigen-Presenting Cells D002454:Cell Differentiation D006801:Humans D007108:Immune Tolerance D054992:Immunological Synapses D016219:Immunotherapy, Adoptive D008213:Lymphocyte Activation D018448:Models, Immunological D020239:Receptor Cross-Talk D016201:Receptors, Lymphocyte Homing D017634:Self Tolerance D058615:Synthetic Biology D050378:T-Lymphocytes, Regulatory D013950:Thymus Gland
regulatory T cells antigen-presenting cells homing suppression immune tolerance