Studies have suggested a benefit of consuming green tea in promoting general health and reducing the risk of certain diseases. However, little is known about the effect of green tea on immune function. In this study we determined the effect of epigallocatechin-3-gallate (EGCG), the major active component of tea, on proliferation of spleen cells isolated from C57BL mice. Results showed that T cell proliferation was inhibited by EGCG at physiologically relevant concentrations of 2.5 to 10 microM. EGCG at these concentrations did not induce cytotoxicity or apoptosis. Oxidative stress is not likely to be responsible for the EGCG-induced suppression of T cell proliferation because H(2)O(2) generation was not significantly different between the cultures supplemented with 1 to 10 microM EGCG and control and catalase did not prevent this EGCG-induced inhibition. Further mechanistic studies showed that EGCG dose dependently inhibited T cell division and cell cycle progression. EGCG supplementation resulted in lower IL-2 receptor expression and higher IL-2 accumulation, suggesting an impeded IL-2/IL-2 receptor signaling. These results indicate that EGCG supplementation may be beneficial to those with abnormally excessive T cell function such as autoimmune and inflammatory disorders, but caution should be taken when it is administered at high doses to those with compromised T cell function.