Modulation of purified murine T cell subset activation by dietary n-3 Polyunsaturated fatty acids

Due to the character of the original source materials and the nature of batch digitization, quality control issues may be present in this document. Please report any quality issues you encounter to digital@library.tamu.edu, referencing the URI of the item.Includes bibliographical references (leaves 94-118).Issued also on microfiche from Lange Micrographics.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