Green tea EGCG suppresses T cell proliferation through impairment of IL-2/IL-2 receptor signaling

Authors: WU, DAYONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; GUO, ZHUYAN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; REN, ZHIHONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; GUO, WEIMIN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University; MEYDANI, SIMIN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Free Radical Biology and Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/1/2009
Publication Date: 9/1/2009
Citation: Wu, D., Guo, Z., Ren, Z., Guo, W., Meydani, S.N. 2009. Green tea EGCG suppresses T cell proliferation through impairment of IL-2/IL-2 receptor signaling. Free Radical Biology and Medicine. 47:636-643.

Interpretive Summary: Tea is a popular beverage and studies suggest that consuming green tea may have several potential health benefits. Catechins are natural substances occurring in tea, thought to be the major components responsible for tea’s beneficial biological effects. These catechins include epicatechin (EC), epigallocatechin (EGC), epicatechin-3-gallate (ECG), and epigallocatechin-3-gallate (EGCG). EGCG is the most biologically active catechin in green tea and accounts for 50 to 80% of the total tea catechins and is, thus, the focus of the majority of published studies. An important mechanism that underlies the major health benefits of consuming EGCG, such as its anti-cancer and anti-inflammation properties, is its ability to suppress cell growth, which has been demonstrated in several different cell types. However, reducing cell growth induced by EGCG may not be limited to the abnormal cells alone, e.g., tumor cells, because the growth of other cells has also been shown to be reduced by EGCG. Given the importance of T cell function in the body’s defense against infection, controlling autoimmune diseases, tumor surveillance, as well as a variety of inflammatory and degenerative disorders, our study focused on the effect of EGCG on T cell function, which has not been well studied to date. In this study, we determined whether EGCG at concentrations (0.5 to 10 microM) affects T cell function and further explored its underlying mechanism. We report that EGCG, at 2.5 microM and above, dose-dependently, inhibited T cell growth by causing cell cycle arrest and consequently, failure of cells to divide. Furthermore, EGCG contributed toward impairing T cell expansion. It thus appears that EGCG may suppress crucial cell-mediated immune response. Furthermore, if EGCG does inhibit T cell function, the underlying mechanism for this action of EGCG has not been clarified. These results may be of benefit to the public and to the medical profession since they 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 conditions in which T cell function is compromised.

Technical Abstract: 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 H2O2 production was lower in the cultures supplemented with 1 to 10 microM EGCG 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, while it did not have an impact on T cell apoptosis. 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.