Effects of dietary n-3 fatty acids on T cell activation and T cell receptor-mediated signaling in a murine model

A short-term feeding paradigm in mice, with diets enriched with eicosapenta enoic acid (EPA) and docosahexaenoic acid (DHA), was used to study the modu lation of T cell activation via the T cell receptor (TcR) and the downstrea m pathways of intracellular signaling. Diets enriched in EPA and DHA suppre ssed antigen-specific delayed hypersensitivity reactions and mitogen-induce d proliferation of T cells. Cocultures of accessory cells and T cells from mice given different diets revealed that purified fatty acid ethyl eaters a cted directly on the T cell, rather than through the accessory cell. The lo ss of proliferative capacity was accompanied by reductions in interleukin ( IL)-2 secretion and IL-2 receptor alpha chain mRNA transcription, suggestin g that dietary EPA and DHA act, in part, by interrupting the autocrine IL-2 activation pathway. Dietary EPA and DHA blunted the production of intracel lular second messengers, including diacylglycerol and ceramide, following m itogen stimulation in vitro. Dietary effects appear to vary with the agonis t employed (i.e., anti-CD3 [TcR], anti-CD28, exogenous LT,-2, or phorbol my ristate acetate and ionomycin).