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 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.
Arrington
J L
JL
Faculty of Nutrition, Texas A&M University, College Station, TX, USA.
McMurray
D N
DN
Switzer
K C
KC
Fan
Y Y
YY
Chapkin
R S
RS
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D018106:CD28 Antigens / Q000187:drug effects / Q000378:metabolism*; D002455:Cell Division; D004032:Diet; D004041:Dietary Fats / Q000494:pharmacology; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D005227:Fatty Acids / Q000494:pharmacology; D015525:Fatty Acids, Omega-3 / Q000378:metabolism; D005260:Female; D005395:Fish Oils / Q000494:pharmacology; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis; D019169:Jurkat Cells; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000166:cytology* / Q000378:metabolism
D018106:CD28 Antigens; D004041:Dietary Fats; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D007376:Interleukin-2; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid