Control of immune homeostasis by naturally arising regulatory CD4+ T cells

CD4+CD25+ regulatory T (TR) cells are essential negative regulators of multiple immune functions. Their development and function are critically dependent on the forkhead transcription factor Foxp3. IL-2R-derived signals are also required for their maturation and/or proliferation. Expression of the TNF receptor family member GITR appears to define this naturally arising, thymically derived lineage more accurately than CD25. TR cells suppress virtually all forms of immune responsiveness investigated to date, including both adaptive and innate immunity. TR cells are capable of robust antigen-driven proliferation in vivo, and may participate in clonal expansion in response to infection, similar to all other adaptive immune lineages.