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Transforming growth factor-β (TGF-β) is a potent regulatory cytokine with diverse effects on hemopoietic cells. The pivotal function of TGF-β in the immune system is to maintain tolerance via the regulation of lymphocyte proliferation, differentiation, and survival. Among T cells, CD4⁺CD25⁺FOXP3⁺ T regs contain the main source of TGF-β that suppresses immune responses in inflammatory sites. Defects in TGF-β1 expression or its signaling in T cells correlate with the onset of several autoimmune diseases. Thus, understanding the function and regulation of TGF-β during immune responses offers therapeutic promise for the control of autoimmune diseases such as multiple sclerosis. However, the main mechanism by which TGF-β exerts its protective effects on the experimental model of multiple sclerosis remains to be elucidated. Paradoxically, TGF-β1 also acts as a pro-inflammatory cytokine and induces interleukin …