Epigallocatechin-3-gallate directly suppresses T cell proliferation through impaired IL-2 utilization and cell cycle progression.
Previously, we demonstrated that in vitro epigallocatechin-3-gallate (EGCG) supplementation inhibited T cell response in mouse spleen cells. In this study, we confirmed this effect of EGCG in mice fed 0.3% EGCG for 6 wk. A coculture with all the combinations of preincubating antigen-presenting cells and T cells with or without EGCG showed that EGCG suppressed antigen-induced T cell proliferation, mainly through a direct effect on T cells. To determine the mechanisms for this effect of EGCG, we stimulated purified mouse T cells with anti-CD3/CD28 in the presence of EGCG (2.5-15 micromol/L) and found that EGCG dose-dependently inhibited cell division and cell cycle progression and this effect of EGCG was more pronounced in CD4(+) than in CD8(+) T cells. Interleukin (IL)-2 concentrations in EGCG-treated cell cultures showed no difference up to 24 h but were higher in the cultures at 48 h compared with the untreated control cells. However, intracellular staining showed no difference between EGCG-treated and untreated control cells in IL-2 synthesis, but EGCG-treated cells expressed less IL-2 receptor (IL-2R) compared with untreated control cells. EGCG did not affect mRNA expression of IL-2 and IL-2R. These results indicate that EGCG-induced IL-2 accumulation in 48 h cultures is due to its reduced utilization. In summary, EGCG directly inhibits T cell proliferative response to both polyclonal and antigen-specific stimulation. CD4(+) cells are more responsive to EGCG than CD8(+) cells. Future studies should determine the effect of EGCG on CD4(+) cell subsets to assess its application in T cell-mediated autoimmune diseases.
Nutritional Immunology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA.
Munkyong
M
Pae
Zhihong
Z
Ren
Mohsen
M
Meydani
Fu
F
Shang
Simin Nikbin
SN
Meydani
Dayong
D
Wu
D000818:Animals; D000911:Antibodies, Monoclonal; D018106:CD28 Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000235:genetics; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology
D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D017252:CD3 Complex; D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D002392:Catechin; C045651:epigallocatechin gallate