Immunosuppressive dietary n-3 polyunsaturated fatty acids differentially modulate costimulatory regulation of murine CD4⁺ T-cell function /
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| Format: | Thesis eBook |
| Language: | English |
| Published: |
[College Station, Tex.] :
[Texas A&M University],
[2005]
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| Subjects: | |
| Online Access: | Link to OAK Trust copy |
| Abstract: | Consumption of fish oils (FO) enriched with the n-3 polyunsaturated fatty acids (PUFA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), is beneficial to a variety of inflammatory disorders due, in part, to the alteration of membrane composition of T-lymphocytes and other immune cells. We previously observed that down-regulation of proliferation and cytokine synthesis by CD4⁺ T-cells in mice fed diets rich in n-3 PUFA was dependent on the involvement of CD28, a co-stimulatory molecule necessary for T-cell activation. Since the co-receptor homologues, CD28 and CTLA-4, have opposing effects on T-cell activation, we hypothesized that the balance of costimulatory and downregulatory properties of CD28 and CTLA-4, respectively, would be altered by diet. A significant increase (p<0.05) in CD28 and CTLA-4 surface expression was observed in CD4⁺ T-cells post-stimulation with phorbol ester and calcium ionophore (PMA/Iono) or anti-CD3 and anti-CD28 ([alpha]CD3/CD28) antibodies in all diet groups. A significant increase (p<0.01; 20%) in the number of CD28 molecules was observed in n-3 PUFA vs. CO-fed mice after 48 h of in vitro CD4⁺ T-cell activation, and both CTLA-4 mRNA transcript and protein levels were upregulated by 50% at 72 h post-activation (p<0.01). Treatment with anti-CTLA-4 mAb in vivo in Mycobacterium bovis (BCG)-vaccinated mice did not alter the suppressive effects of dietary n-3 PUFA on antigen (PPD)-induced lymphocyte proliferation or delayed hypersensitivity reactions. Ligation of CD28 upregulates IL-10 receptor (IL-10R) expression on CD4⁺ T-cells. Therefore, we hypothesized that dietary n-3 PUFA would suppress T-cell function through the effects of IL-10. Surprisingly, the proliferation of purified splenic CD4⁺ T-cells activated in vitro with [alpha]CD3/CD28 was suppressed by dietary n-3 PUFA in both conventional mice (C57BL/6) and IL-10 gene knockout (IL-10-/-) mice. Furthermore, IL-10R cell surface expression was significantly down-regulated on CD4⁺ T-cells from both the C57BL/6 and IL-10[superscript -/-] mice fed dietary n-3 PUFA after 72 h of in vitro stimulation with [alpha]CD3/CD28. CD4⁺ T-cells from C57BL/6 mice fed DHA produced significantly less IFN[gamma] and IL-10, while CD4⁺ T-cells from IL-10[superscript -/-] mice fed dietary n-3 PUFA produced significantly more IFN[gamma] compared to the CO-fed group. |
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| Item Description: | "Major Subject: Nutrition" Title from author supplied metadata (automated record created on Feb. 17, 2005.) Vita. Abstract. Electronic resource. |
| Format: | Mode of access: World Wide Web. System requirements: World Wide Web access and Adobe Acrobat Reader. |
| Bibliography: | Includes bibliographical references. |