Docosahexaenoic acid suppresses function of the CD28 costimulatory membrane receptor in primary murine and Jurkat T cells

(n-3) Polyunsaturated fatty acids (PUFA) have been widely documented to red uce inflammation in diseases such as rheumatoid arthritis. This study sough t to elucidate the mechanism whereby (n-3) PUFA downregulate T-cell prolife ration. We hypothesized that membrane incorporation of dietary PUFA would a lter membrane structure and consequently membrane receptor function. Female C57BL/6 mice were fed for 14 d one of three diets containing arachidonic a cid (AA), fish oil or docosahexaenoic acid (DHA) that varied in lipid compo sition only. Spleens were harvested and T cells (similar to 90% purity) wer e activated with agonists that stimulated proliferation at the receptor lev el [anti-CD3 (alpha CD3)/anti-CD28 (alpha CD28)], intracellularly [phorbol- 12-myristate-13-acetate (PMA)/ionomycin] or with a combined receptor/intrac ellular agonist (alpha CD3/PMA). Although there was no significant differen ce (P > 0.05) in proliferative response across dietary groups within each a gonist set, interleukin (IL)-2 secretion was significantly reduced (P = 0.0 5) in cells from DHA-fed mice stimulated with (alpha CD3/(alpha CD28, In pa rallel in vitro experiments, Jurkat T cells were incubated with 50 mu mol/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 secre tion 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 A A. The results of this study suggest the involvement of the CD28 receptor i n reducing IL-2 secretion in DHA-fed mice and DHA-incubated Jurkat cells an d that purified T cells from DHA-fed mice require accessory cells to modula te proliferative suppression.