What regulates regulatory T cells?
Regulatory T cells prevent excessive immune reactions. In autoimmune disease, regulatory T cell deficiency can allow the immune system to attack the body's own tissues. In cancer, excessive activity of regulatory T cells prevents the immune system from destroying cancer cells. Foxp3+ (forkhead box P3) T cells are regulatory cells that are critical for controlling the degree of immune activation during infection, autoimmunity and allergy. These cells are important for self / non-self- discrimination. The EU-funded TREG (Analysis of regulatory T cell proliferation and apoptosis in vivo at the cellular and molecular level) project was dedicated to elucidating mechanisms regulating Foxp3+ T cells. TREG used genetic models to study proliferation and apoptosis during expansion, contraction and homeostatic stages. Scientists identified Mcl-1 (induced myeloid leukemia cell differentiation protein) as a primary factor for regulatory T cell homeostasis, making it a potential drug target. Interleukin 2 (IL-2) affected both Mcl1 and T cell survival. Experiments revealed that the apoptotic proteins Bax, Bak and Bim are the key regulators of circulating Foxp3+ T cells. Interestingly, Bcl-2 (B-cell lymphoma 2) proteins hardly played any role in controlling regulatory T cell homeostasis. TREG analysed the kinetics of regulatory T cell response in connection with disturbed homeostasis. Project outcomes resulted in two patent applications. Understanding the factors controlling regulatory T cell numbers is the first step to make this process amenable to therapeutic manipulation. The results will have important implications for patients suffering from autoimmune disease.
