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Modulation of purified murine T cell subset activation by dietary n-3 Polyunsaturated fatty acids
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n-3 Polyunsaturated fatty acids (PUFA) have been shown to reduce inflammation in diseases such as rheumatoid arthritis. The present studies sought to elucidate mechanisms whereby n-3 PUFAs downregulate T cell proliferation and affect CD4 and CD8 T cell activation. We hypothesized that membrane incorporation of dietary PUFA would alter membrane structure and consequently membrane receptor function, and that PUFA would differentially modulate CD4 and CD8 T cell activation via receptor-mediated events. In the whole T cell study, female C57BL/6 mice were fed one of three diets, that varied by lipid composition only, containing either arachidonic acid (AA), fish oil (FO), or docosahexaenoic acid (DHA) for 14 d. Splenic T cells (~90% purity) were activated with agonists that stimulated proliferation at either the receptor level (αCD3/αCD28), intracellularly (PMA/Ionomycin), or with a combination of receptor/intracellular agonists (αCD3/PMA). IL-2 secretion was significantly reduced in cells from DHA-fed animals stimulated with αCD3/αCD28. In parallel in vitro experiments, Jurkat T cells were incubated with 50uM linoleic acid (LA), AA, or DHA, and stimulated with similar agonist sets. Cells incubated with DHA and AA exhibited significantly reduced IL-2 secretion, however, only when the CD28 receptor was engaged. In the T cell subset studies, diets varied by lipid composition only containing either safflower oil (SAF), FO, or an eicosapentaenoic/docosahexaenoic (EPA/DHA) acid combination. Splenic CD4 T cells (~90% purity) or CD8 T cells (~85% purity) were activated with the agonists described above. Analysis of IL-2 and IL-4 secretion revealed that the CD4 T cells stimulated with αCD3/αCD28 or PMA/Ionomycin were of the Th1 phenotype whereas those stimulated with αCD3/PMA were of the Th2 phenotype. Proliferation of Th2 CD4 cells varied by diet, with SAF<EPA/DHA<FO. Additionally, IL-2 production by αCD3/αCD28 stimulated CD4 T cells was significantly reduced in FO-fed animals. The αCD3/αCD28 stimulated CD8 cells cultured from FO-fed animals exhibited a significant decrease in proliferation. The results of these two studies suggest the involvement of the CD28 and/or CD3 receptor in dietary n-3 PUFA-mediated T cell regulation. Furthermore, our results suggest that dietary n-3 PUFA are capable of differentially modulating T cell subset function.
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Includes bibliographical references (leaves 94-118).
Issued also on microfiche from Lange Micrographics.
Arrington, Jennifer L (2000). Modulation of purified murine T cell subset activation by dietary n-3 Polyunsaturated fatty acids. Master's thesis, Texas A&M University. Available electronically from
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