The phytogestrogenic stilbenes, arachidin-1 and resveratrol, modulate regulatory T cell functions responsible for successful aging in aged ICR mice

CD4+CD25+ regulatory T cells (Tregs) are recognized as a distinctive T helper cell population which controls immunosuppression during the maintenance of immunological self-tolerance and immunohomeostasis. Sex steroids modulate fundamental immune functions, including immune cell development, differentiation and polarization, and facilitate specific immunophysiological microenvironments, such as pregnancy. The supplementation of exogenous phytoestrogens is beneficial to post-menopausal women. Stilbenes are a potent group of phytoestrogens, of which resveratrol (Res) is a well-known representative exhibiting a variety of immunomodulatory activities, including the attenuation of autoimmune diseases and boosting anti-tumor immunity. In the present study, arachidin-1 (Ara-1) and Res, primary stilbenes, enriched in peanut sprouts as phytoalexins, were investigated for their immunomodulatory properties for successful aging. We found that similar to 17-β-estradiol (E2), Ara-1 or Res significantly inhibited concanavalin A (ConA)-activated lymphoblastogenesis of cell repertories from splenic or thymic origins. However, these inhibitory effects were partially reversed by the E2 receptor blocker, tamoxifen. While the ratios of the CD4+CD25+ cell population of ConA-activated T cell repertories were not significantly altered, treatment with E2, Ara-1 or Res led to an increase in the number of cytotoxic T-lymphocyte associated protein 4 (CTLA-4; also known as CD152)-positive cells and in the gene expression levels of CTLA-4, Forkhead box P3 (FoxP3), interleukin (IL)-10 and transforming growth factor-β (TGF-β). When low (L-S-PNT) and high (H-S-PNT) levels of stilbene-enriched peanut sprout-fortified diets were provided ad libitum to 12-week-old ICR mice for 48 weeks, their circulating Treg populations were assessed following magnetic bead enrichment. The gene expression levels of CTLA-4 and TGF-β were significantly (P