Abstract: Compositions and methods for modulation of the suppressive activity of CD4+CD25+regulatory T cells (Treg) on CD4+CD25? effector T cells (Teff) are provided. An agent selected from: (i) dopamine; (ii) a dopamine precursor; (iii) a D1-R agonist; (iv) a D2-R antagonist; (v) a combination of (i) and (ii); or (vi) a combination of (i), (ii) or (iii) with (iv), down-regulates the suppressive activity of Treg and is useful for treatment of cancer. An agent selected from (i) a dopamine D2-R agonist, (ii) a dopamine D1-R antagonist, and (iii) a combination of (i) and (ii), up-regulates the suppressive activity of Treg and is useful for treatment of an autoimmune disease or for controlling graft rejection in tissue/organ transplantation.