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Title: Epigallocatechin-3-gallate directly suppresses T cell proliferation through impaired IL-2 utilization and cell cycle progression

Author
item PAE, MUNKYONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item MEYDANI, MOHSEN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item SHANG, FU - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item MEYDANI, SIMIN - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item WU, DAYONG - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/20/2010
Publication Date: 7/1/2010
Citation: Pae, M., Meydani, M., Shang, F., Meydani, S.N., Wu, D. 2010. Epigallocatechin-3-gallate directly suppresses T cell proliferation through impaired IL-2 utilization and cell cycle progression. Journal of Nutrition. 140:1509-1515.

Interpretive Summary: Green tea promotes good health and helps prevent some disease. Its effect on the immune system, however, has not been studied well. Most studies have been done in the laboratory on cells and not in animals or humans (in vivo). Many of the studies use supplementation with tea extracts or the isolated catechins. In general, epigallocatechin-3-gallate (EGCG), the most abundant and bioactive catechin in green tea, suppresses the proliferation of a variety of immune-system cells (such as T cells), which are important in the body’s defense system. It is not clear if EGCG’s effect is directly on the immune cells or indirectly on accessory cells that facilitate proliferation of T cells themselves. In this study, we used healthy mice to test the effect of EGCG on immune cell response and T cell function. Our results show that a high intake of EGCG suppresses T cell proliferation by causing an arrest of the cell cycle. This suggests that the T cell suppressive effect of EGCG might have potential application in treating autoimmune diseases in which the immune system is overactive or mis-directed to the extent that it attacks the body’s own cells resulting in impairment to several body systems.

Technical Abstract: Epigallocatechin-3-gallate (EGCG), a bioactive component of green tea, has a variety of health impact. Previously we demonstrated that in vitro EGCG supplementation inhibited T cell response in mouse spleen cells. In the present study, we first extended our in vitro observation to in vivo and confirmed the suppressive effect of dietary EGCG supplementation on T cell proliferation in mice fed 0.3 percent EGCG for 6-wk. Next we determined the direct effect of EGCG on T cells and its mechanisms. Purified T cells from C57BL/6 mice were stimulated with anti-CD3/CD28 in the presence of EGCG (2.5-15 micromol/L). EGCG dose-dependently inhibited cell division, which was more pronounced in CD4+ than CD8+ T cells. EGCG induced cell cycle arrest as fewer cells entered S-G2-M phase. Since interleukin (IL)-2 is a key factor for T cell proliferation, we determined effect of EGCG on IL-2 and IL-2 receptor (IL-2R, CD25). Surprisingly, EGCG-treated T cell cultures had more IL-2. Although EGCG treatment slightly increased the percentage of IL-2+ cells in CD8+ but not CD4+ population, it reduced average IL-2 production per cell in both CD8+ and CD4+ cells. EGCG did not affect percentage of IL-2R-expressing T cells but reduced IL-2R expression per cell. EGCG had no effect on mRNA expression of IL-2 and IL-2R. Together, our results indicate that high intake of EGCG inhibits T cell proliferation by inducing cell cycle arrest, which is in turn due to impaired IL-2/IL-2R signaling. T cell-suppressive effect of EGCG may have a potential application in T cell-mediated autoimmune diseases.