The effect of dietary n-3 polyunsaturated fatty acids on T cell subset activation-induced cell death

Show full item record

Title: The effect of dietary n-3 polyunsaturated fatty acids on T cell subset activation-induced cell death
Author: Switzer, Kirsten Collette
Abstract: Dietary 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 .
URI: http : / /hdl .handle .net /1969 .1 /1097
Date: 2004-11-15

Citation

The effect of dietary n-3 polyunsaturated fatty acids on T cell subset activation-induced cell death. Available electronically from http : / /hdl .handle .net /1969 .1 /1097 .

Files in this item

Files Size Format View
etd-tamu-2004B-NUTR-Switzer-2.pdf 1.730Mb application/pdf View/Open

This item appears in the following Collection(s)

Show full item record

Search DSpace

Advanced Search

Browse