J. Lipid Res.
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A more recent version of this article appeared on August 1, 2004

Papers In Press, published online ahead of print May 16, 2004
J. Lipid Res., doi:10.1194/jlr.M400028-JLR200
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Submitted on January 26, 2004
Revised on April 13, 2004
Accepted on May 2, 2004

Dietary n-3 polyunsaturated fatty acids promote activation-induced cell death in Th1-polarized murine CD4+ T cells

Kirsten C. Switzer, Yang-Yi Fan, Naisyin Wang, David N. McMurray, and Robert S. Chapkin

Faculty of Nutrition, Texas A&M University, College Station, TX 77843-2471

Corresponding Author: r-chapkin{at}tamu.edu

Dietary n-3 polyunsaturated fatty acids (PUFA) have been shown to attenuate T cell-mediated inflammation. To investigate whether dietary n-3 PUFA promote activation-induced cell death (AICD) in CD4+ T cells induced in vitro to a polarized Th1 phenotype, C57BL/6 mice were fed diets containing either 5% corn oil (n-6 PUFA control) or 4% fish oil + 1% corn oil (n-3 PUFA) for 2 wk. Splenic CD4+ T cells were cultured with alpha IL-4, IL-12, and IL-2 for 2 d and then rIL-12 and rIL-2 for 3 d in the presence of diet-matched homologous mouse serum (MS) to prevent loss of cell membrane fatty acids, or fetal bovine serum. Following polarization, Th1 cells were reactivated and analyzed for IFNgamma and IL-4 by intracellular cytokine staining, and for apoptosis by Annexin V/PI. Dietary fish oil (FO) enhanced Th1 polarization by 49% (p=0.0001) and AICD by 24% (p=0.0001) only in cells cultured in the presence of MS. FO enhancement of Th1 polarization and AICD following culture was associated with the maintenance of EPA (20:5n-3) and DHA (22:6n-3) in plasma membrane lipid rafts. In conclusion, n-3 PUFA enhance the polarization and deletion of proinflammatory Th1 cells, possibly as a result of alterations in membrane microdomain fatty acid composition.


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