These lymphokines are capable of inhibiting activation of Th1, Th2 cells and CTLs required for cell-mediated immunity, inflammation and antibody production. Certain recent experimental data and results even indicate that IL-2-IL-2R signaling is vital for development, maintenance, survival, expansion and suppressive activity of Tregs. Increased expression of certain other characteristic markers including CTLA-4, glucocorticoid-inducible tumor necrosis factor receptor (GITR) and OX40 has been identified on Tregs whose function inside these cells is still not clear. The TCRs displayed on Tregs are capable of recognizing and interacting with any peptide-MHC class II ligand having certain range of avidity. But, the contribution of TCR signaling and role of TCR-ligand interactions towards regulatory T-cell development needs to be determined. It is almost impossible to discriminate between the natural Tregs and adaptive Tregs. Through a series of experiments conducted in transgenic mice and through retroviral over expression studies, researchers have identified FoxP3 to be a specific molecular marker essential for the development and function of Tregs. The primary evidence regarding the involvement of FoxP3 in the development of Tregs was provided by the experiments of Sakaguchi et.al in patients suffering from IPEX, a rare and fatal human autoimmune disorder. In these patients, mutated FoxP3 gene causes improper development of Tregs resulting in hyperactivation of T-cells reactive to self-antigens. Recently, experiments have clearly shown that retroviral mediated introduction of FoxP3 into conventional CD4+ T-cells converts them into regulatory T-cells. Although the emergence of regulatory T-cells and the role of FoxP3 as a critical player in their development holds great promise for the development of novel therapies for the treatment of autoimmune diseases in humans, there are several questions that remain to be answered. These include further investigation into the basic biology of Tregs, including identification of ligands responsible for thymic selection of these cells, and elucidation of the exact role of FoxP3 relative to the various markers present on Tregs and most importantly the effector mechanisms by which Tregs exert their suppressive effects. A better understanding of manipulating FoxP3 and Tregs will enable us to harness the tremendous therapeutic potential in various clinical situations including Type I diabetes, Multiple sclerosis, GVHD, rheumatoid arthritis and allergy.