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Articles

Docosahexaenoic Acid Suppresses Function of the CD28 Costimulatory Membrane Receptor in Primary Murine and Jurkat T Cells¹

Jennifer L. Arrington^*, David N. McMurray^*,,**, Kirsten C. Switzer^*, Yang-Yi Fan^* and Robert S. Chapkin^*,**2

^* Faculty of Nutrition, Department of Medical Microbiology and Immunology and the ^** Center for Environmental and Rural Health, Texas A&M University, College Station, TX

²To whom correspondence should be addressed. E-mail: r-chapkin{at}tamu.edu.

(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 (90% purity) were activated with agonists that stimulated proliferation at the receptor level [anti-CD3 (CD3)/anti-CD28 (CD28)], intracellularly [phorbol-12-myristate-13-acetate (PMA)/ionomycin] or with a combined receptor/intracellular agonist (CD3/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 CD3/CD28. In parallel in vitro experiments, Jurkat T cells were incubated with 50 µmol/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.

KEY WORDS: • T cell • Jurkat cell • docosahexaenoic acid • fish oil • arachidonic acid • mice

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