Nucleotide-free diet suppresses antigen-driven cytokine production by primed T cells: Effects of supplemental nucleotides and dietary fatty acids

Abstract

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. IFNγ 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. IFNγ 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 IFNγ 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.