Dietary n-3 polyunsaturated fatty acids modulate purified murine T-cell subset activation

Studies in humans and murine disease models have clearly shown dietary fish oil to possess anti-inflammatory properties, apparently mediated by the n- 3 polyunsaturated fatty acids, eicosapentaenoic acid (EPA) and docosahexaen oic acid (DHA). To determine the mechanisms by which dietary EPA and DHA mo dulate mouse T-cell activation, female C57BL/6 mice were fed diets containi ng either 2% safflower oil (SAF), 2% fish oil (FO), or a 2% purified EPA/DH A ethyl ester mixture for 14 days. Splenic CD4 T cells (similar to 90% puri ty) or CD8 T cells (similar to 85% purity) were incubated with agonists whi ch act at the plasma membrane receptor level [anti(alpha)-CD3/anti(alpha)-C D28], the intracellular level (PMA/Ionomycin), or at both the receptor and intracellular levels (alpha CD3/PMA). CD4 T cells stimulated with alpha CD3 /alpha CD28 or PMA/Ionomycin proliferated and produced principally IL-2 (i. e. a Th1 phenotype), whereas the proliferation of CD4 T cells stimulated wi th alpha CD3/PMA was apparently driven principally by IL-4 (i.e. a Th2 phen otype). The IL-4 driven proliferation of putative Th2 CD4 cells was enhance d by dietary n-3 fatty acids (P = 0.02). Conversely, IL-2 production by alp ha CD3/alpha CD28-stimulated CD4 T cells was reduced in FO-fed animals (P < 0.0001). The alpha CD3/alpha CD28-stimulated CD8 cells cultured from FO-fe d animals exhibited a significant decrease (P < 0.05) in proliferation. The re were no dietary effects seen in alpha CD3/PMA-stimulated CD8 cells, whic h produced both IL-2 and IL-4, or in PMA/Ionomycin-stimulated CD8 cells, wh ich produced principally IL-2. These data suggest that dietary n-3 fatty ac ids down-regulated IL-2 driven CD4 and CD8 activation, while up-regulating the activation of the Th2 CD4 T-cell subset. Thus, the anti-inflammatory ef fects of n-3 fatty acids may result in both the direct suppression of IL-2- induced Th1 cell activation and the indirect suppression of Th1 cells by th e enhanced cross-regulatory function of Th2 cells.