Nucleotide-free diet suppresses antigen-driven cytokine production by primed T cells: effects of supplemental nucleotides and dietary fatty acids.
Our previous studies suggest that nucleotides modulate T-helper (Th) cell-mediated antibody (Ab) production. This nucleotide action is influenced by dietary fatty acids. Herein, we report the effects of nucleotide-free (NF) diets normal or high in saturated fatty acid on antigen-driven Th cell activation by using cytokine production as an indicator. C57BL/6 mice were fed a NF diet, a NF diet plus mononucleotide and nucleoside mixture (OG-VI), a NF diet high in saturated fatty acid (NF-SFA), or a NF-SFA diet plus OG-VI. Mice were then challenged with neoantigen, a keyhole limpet hemocyanin (KLH). Regional draining lymph nodes were collected 5-7 d following antigen (AG) priming, rechallenged with KLH in the culture, and resultant cytokine production was measured. IFN gamma and IL-5 production was lower in mice fed a NF diet at protein and mRNA levels. IL-4 and IL-2 mRNA expression was also lower in mice fed a NF diet. IFN gamma protein levels were higher in mice fed a NF-SFA diet than in mice fed a NF diet, but production of other cytokines was equally suppressed in those fed a NF-SFA diet. In vivo OG-VI supplementation prevented aberrant cytokine production in mice fed a NF or NF-SFA diet. Polynucleotides added to the culture restored impaired IFN gamma and IL-5 production in mice fed a NF diet but did not further augment cytokine production in mice of other diet groups. These results indicate a potential role of nucleotides in Ag-driven Th-cell activation, and this nucleotide action is partly under the influence of dietary fatty acids.
Jyonouchi
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Department of Pediatrics, University of Minnesota, Minneapolis 55455, USA.
Sun
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Sato
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D000818:Animals; D000941:Antigens / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004032:Diet; D005227:Fatty Acids / Q000008:administration & dosage*; D005260:Female; D006433:Hemocyanins / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D015848:Interleukin-5 / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D009711:Nucleotides / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
D000941:Antigens; D016207:Cytokines; D005227:Fatty Acids; D007376:Interleukin-2; D015848:Interleukin-5; D009711:Nucleotides; D012333:RNA, Messenger; D015847:Interleukin-4; D007371:Interferon-gamma; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin