Dietary eicosapentaenoic acid modulates CTLA-4 expression in murine CD4+ T-cells.
We have demonstrated that downregulation of proliferation by CD4(+) T-cells in mice fed n-3 PUFA diets is dependent on the involvement of CD28. Therefore, we hypothesized that the balance of co-stimulatory and downregulatory properties of CD28 and CTLA-4, respectively, would be altered by diet. Mice were fed a control corn oil (CO)-enriched diet devoid of n-3 PUFA, or diets enriched with either docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) for 14d. The proliferation of splenic CD4(+) T-cells was suppressed by DHA and EPA following stimulation with anti-CD3 and anti-CD28. Surprisingly, the number of surface CD28 molecules was not reduced in activated CD4(+) T-cells from either group of n-3 PUFA-fed mice. However, in mice fed EPA, CTLA-4 protein levels were enhanced significantly 72 h post-activation (P<0.01). Therefore, we conclude that dietary EPA may suppress CD4(+) T-cell activation by enhancing the downregulatory co-receptor CTLA-4, while not altering the levels of CD28.
Ly
Lan H
LH
Department of Nutrition and Food Science, Texas A&M University System Health Science Center, College Station, TX, USA.
Smith
Roger
R
Switzer
Kirsten C
KC
Chapkin
Robert S
RS
McMurray
David N
DN
D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism*; D018106:CD28 Antigens / Q000235:genetics / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D060908:CTLA-4 Antigen; D049109:Cell Proliferation / Q000187:drug effects; D003314:Corn Oil / Q000494:pharmacology; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage / Q000494:pharmacology*; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D005227:Fatty Acids / Q000032:analysis; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors
D015703:Antigens, CD; D000943:Antigens, Differentiation; D018106:CD28 Antigens; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D004042:Dietary Fats, Unsaturated; D005227:Fatty Acids; D015525:Fatty Acids, Omega-3; D012333:RNA, Messenger; D004281:Docosahexaenoic Acids; D003314:Corn Oil; D015118:Eicosapentaenoic Acid