Docosahexaenoic acid suppresses function of the CD28 costimulatory membrane receptor in primary murine and Jurkat T cells.
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abstract
(n-3) polyunsaturated fatty acids (PUFA) have been widely documented to reduce inflammation in diseases such as rheumatoid arthritis. This study sought to elucidate the mechanism whereby (n-3) PUFA downregulate T-cell proliferation. We hypothesized that membrane incorporation of dietary PUFA would alter membrane structure and consequently membrane receptor function. Female C57BL/6 mice were fed for 14 d one of three diets containing arachidonic acid (AA), fish oil or docosahexaenoic acid (DHA) that varied in lipid composition only. Spleens were harvested and T cells ( approximately 90% purity) were activated with agonists that stimulated proliferation at the receptor level [anti-CD3 (alphaCD3)/anti-CD28 (alphaCD28)], intracellularly [phorbol-12-myristate-13-acetate (PMA)/ionomycin] or with a combined receptor/intracellular agonist (alphaCD3/PMA). Although there was no significant difference (P > 0.05) in proliferative response across dietary groups within each agonist set, interleukin (IL)-2 secretion was significantly reduced (P = 0.05) in cells from DHA-fed mice stimulated with alphaCD3/alphaCD28. In parallel in vitro experiments, Jurkat T cells were incubated with 50 micromol/L linoleic acid, AA, or DHA. Similar agonists sets were employed, and cells incubated with DHA and AA had a significantly reduced (P < 0.05) IL-2 secretion in three of the agonist sets. However, only when the CD28 receptor was stimulated was there a significant difference (P < 0.05) between DHA and AA. The results of this study suggest the involvement of the CD28 receptor in reducing IL-2 secretion in DHA-fed mice and DHA-incubated Jurkat cells and that purified T cells from DHA-fed mice require accessory cells to modulate proliferative suppression.
