FOXP3+ Regulatory T Cells: Control of FOXP3 Expression by Pharmacological Agents

Naturally arising CD4(+)CD25(+) regulatory T cells (Tregs), which specifically express the forkhead family transcription factor FOXP3, are essential for the maintenance of immunological self-tolerance and immune homeostasis. Tregs can suppress the activation, proliferation and effector function of other lymphocytes in physiological and pathological immune responses. Therefore, control of the development, survival, and function of Tregs is instrumental for effective control of immune responses. For example, cytokines such as interleukin-2 and transforming growth factor-β, monoclonal antibodies to the Treg-associated molecules such as interleukin-2 receptor α chain and cytotoxic T lymphocyte-associated 4, and pharmacological agents that alter signaling pathways for Treg function, can augment or dampen the suppressive activity of Tregs. How these agents control the function of Tregs at the molecular level remains to be elucidated. However, it is envisaged that pharmacological control of the function and development of Tregs by targeting FOXP3 or Treg-associated molecules will enable better control of immune responses in various clinical settings.