Autoimmune diseases are common, disabling immune disorders affecting millions of people. Recent studies indicate that dysregulated balance of different CD4+ T-cell subpopulations plays a key role in immune pathogenesis of several major autoimmune diseases. Green tea and its active ingredient, epigallocatechin-3-gallate (EGCG), have been shown to modulate immune cell functions and improve some autoimmune diseases in animal models. In a series of studies we determined EGCG's effect on T-cell functions and its application in autoimmune diseases. We first observed that EGCG inhibited CD4+ T-cell expansion induced by polyclonal (mitogens or anti-CD3/CD28) or antigen-specific stimulation. We then showed that EGCG suppressed expansion and cell cycle progression of naïve CD4+ T by modulating cell cycle-related proteins. EGCG also inhibited naive CD4+ T-cell differentiation into Th1 and Th17 effector subsets by impacting their respective signaling transducers and transcription factors. These results suggest that EGCG may improve T-cell-mediated autoimmune diseases. Using the experimental autoimmune encephalomyelitis (EAE) mice, an animal model for human multiple sclerosis, we found that dietary supplementation with EGCG attenuated the disease's symptoms and pathology. These EGCG-induced changes are associated with findings in the immune and inflammation profiles in lymphoid tissues and the central nervous system: a reduction in proliferation of autoreactive T cells, production of proinflammatory cytokines, and Th1 and Th17 subpopulations, and an increase in regulatory T-cell populations. These results suggest that green tea or its active components may have a preventive and therapeutic potential in dealing with T-cell-mediated autoimmune diseases. However, the translational value of these findings needs to be validated in future human studies.