LAUSR

A number of polyphenolic compounds present in fruits and vegetables have the capacity to modulate immune responses; however, the impact of the common plant‐derived flavonoid myricetin on T lymphocyte function has not been investigated. We show that myricetin inhibited mouse T lymphocyte activation by bead‐immobilized anti‐CD3 and anti‐CD28 monoclonal antibodies, as indicated by a dose‐dependent reduction in cell proliferation and decreased synthesis of interferon‐γ, interleukin (IL)‐2, IL‐4, and IL‐17 associated with different T helper cell subsets. This effect was attributed to myricetin‐induced reactive oxygen species (ROS) since myricetin caused hydrogen peroxide (H2O2) to accumulate in cell‐free culture medium and H2O2 inhibited T cell proliferation and cytokine synthesis. In addition, the antioxidant N‐acetyl cysteine restored the ability of myricetin‐treated T lymphocytes to proliferate in response to a mitogenic stimulus. The presence of dendritic cells or bone marrow‐derived macrophages negated the inhibitory effect of myricetin on T cell activation, and H2O2 in T cell cultures that were treated with exogenous H2O2 was reduced when antigen‐presenting cells were also present. These findings suggest that antioxidant molecules produced by dendritic cells and macrophages protected T cells from myricetin‐induced oxidative stress, and underscore the importance of considering immune cell interactions when evaluating the immunomodulatory activity of ROS‐generating phytochemicals.