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dc.contributor.advisorMcMurray, David N.
dc.contributor.advisorChapkin, Robert S.
dc.creatorSwitzer, Kirsten Collette
dc.date.accessioned2004-11-15T19:46:10Z
dc.date.available2004-11-15T19:46:10Z
dc.date.created2004-08
dc.date.issued2004-11-15
dc.identifier.urihttp://hdl.handle.net/1969.1/1097
dc.description.abstractDietary n-3 polyunsaturated fatty acids (PUFA) have been shown to potently attenuate T cell-mediated inflammation, in part, by suppressing T cell activation and proliferation. Apoptosis is an important mechanism for preventing chronic inflammation by maintaining T cell homeostasis through the contraction of populations of activated T cells. We hypothesized that dietary n-3 PUFA would promote T cell apoptosis, thus, providing an additional mechanism to explain the anti-inflammatory effects. We specifically examined activation-induced cell death (AICD) since it is the form of apoptosis associated with peripheral T cell deletion involved in immunological tolerance and T cell homeostasis. Female C57BL/6 mice were fed diets containing either n-6 PUFA (control) or n-3 PUFA for 14 d. Splenic T cells were stimulated with CD3/CD28, CD3/PMA, or PMA/Ionomycin for 48 h followed by reactivation with the same stimuli for 5 h. Apoptosis was measured using Annexin V/propidium iodide and flow cytometry. Cytokine analyses revealed that n-3 PUFA enhanced AICD only in T cells expressing a Th1-like cytokine profile (high IFN, low IL-4) compared to mice fed the n-6 PUFA control diet. Dietary n-3 PUFA significantly altered the fatty acid composition of phosphatidylcholine and phosphatidylethanolamine in T cell membranes. To examine the apparently selective effect of dietary n-3 PUFA on AICD in Th1 cells, CD4+ T cells were polarized in vitro to a Th1 phenotype by culture with IL-4, IL-2, and IL-12 for 2 d, followed by culture with IL-2 and IL-12 for 3 d in the presence of diet-matched homologous mouse serum (MS) to prevent loss of cell membrane fatty acids. Following polarization and reactivation, we observed that n-3 PUFA enhanced Th1 polarization and AICD only in cells cultured in the presence of MS, but not in fetal bovine serum. The n-3 PUFA enhancement of Th1 polarization and AICD was associated with the maintenance of diet-induced changes in EPA (20:5n-3) and DHA (22:6n-3) in plasma T cell membrane lipid rafts. Overall, these results suggest that dietary n-3 PUFA enhance both the polarization and deletion of pro-inflammatory Th1 cells, possibly as a result of alterations in lipid raft fatty acid composition.en
dc.format.extent1730976 bytesen
dc.format.extent369840 bytesen
dc.format.mediumelectronicen
dc.format.mimetypeapplication/pdf
dc.format.mimetypetext/plain
dc.language.isoen_US
dc.publisherTexas A&M University
dc.subjectactivation-induced cell deathen
dc.subjectapoptosisen
dc.subjectdocosahexaenoic aciden
dc.subjecteicosapentaenoic aciden
dc.subjectfish oilen
dc.subjectlipid raftsen
dc.subjectn-3 polyunsaturated fatty acidsen
dc.subjectT cellen
dc.subjectT helper 1 cellen
dc.titleThe effect of dietary n-3 polyunsaturated fatty acids on T cell subset activation-induced cell deathen
dc.typeBooken
dc.typeThesisen
thesis.degree.departmentAnimal Scienceen
thesis.degree.disciplineNutritionen
thesis.degree.grantorTexas A&M Universityen
thesis.degree.nameDoctor of Philosophyen
thesis.degree.levelDoctoralen
dc.contributor.committeeMemberLupton, Joanne R.
dc.contributor.committeeMemberSmith, Roger, III
dc.type.genreElectronic Dissertationen
dc.type.materialtexten
dc.format.digitalOriginborn digitalen


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