Jyonouchi H, Sun S, Winship T, Kuchan M J
Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA.
J Nutr. 2001 Apr;131(4):1165-70. doi: 10.1093/jn/131.4.1165.
Dietary ribonucleotides have been shown to augment type 1 T-helper cell (Th1) responses to a protein antigen (Ag) in Th1-prone C57BL/6 mice, but their effects on type 2 Th (Th2)-prone mice are unknown. BALB/cJ mice have skewed Th2 responses against ovalbumin (OVA), characterized by augmented production of Th2 cytokines and immunoglobulin (Ig)G1/IgE antibodies (Ab); Th1 responses augment IgG2a Ab production, whereas Th2 responses augment IgG1/IgE Ab production. In this study, we determined the effects of dietary ribonucleotides obtained from yeast on the balance of Th1/Th2 responses against OVA in young BALB/cJ mice. Mice were fed a ribonucleotide-free (NF) or ribonucleotide-supplemented (NS) diet (4.74 g nucleotides/kg diet) and given OVA (10 microg/dose) with incomplete Freund's adjuvant (IFA) at 3 and 6 wk. We assessed T-cell responses in the regional draining lymph nodes (LN) by measuring production and expression of Th1/Th2 cytokines, interferon-gamma (IFN-gamma) and interleukin-5 (IL-5), respectively. Anti-OVA IgG subclass and IgE Ab levels were determined 3 wk after the first OVA challenge and 5 d and 2 wk after the second OVA challenge. Dietary ribonucleotides significantly augmented OVA-specific IFN-gamma production by the regional draining LN cells after the first and second OVA challenges. The NS diet increased anti-OVA IgG2a Ab levels after the first OVA challenge and both anti-OVA IgG2a and anti-OVA IgG2b after the second challenge. OVA-specific IgG1 and IgE Ab levels were lower (P < 0.05) after the second OVA challenge in mice fed the NS diet. Dietary ribonucleotides did not affect production or expression of IL-5. Our findings thus indicate that in Th2-prone BALB/c J mice, dietary ribonucleotides modulated skewed Th2 responses against OVA toward Th1 as measured by production of IFN-gamma, a Th1 cytokine, and changes in anti-OVA Ab isotype levels.
已证明膳食核糖核苷酸可增强Th1倾向的C57BL/6小鼠对蛋白质抗原(Ag)的1型辅助性T细胞(Th1)反应,但其对Th2倾向小鼠的影响尚不清楚。BALB/cJ小鼠对卵清蛋白(OVA)的Th2反应偏向一侧,其特征是Th2细胞因子和免疫球蛋白(Ig)G1/IgE抗体(Ab)产生增加;Th1反应增加IgG2a Ab产生,而Th2反应增加IgG1/IgE Ab产生。在本研究中,我们确定了从酵母中获得的膳食核糖核苷酸对年轻BALB/cJ小鼠针对OVA的Th1/Th2反应平衡的影响。给小鼠喂食无核糖核苷酸(NF)或补充核糖核苷酸(NS)的饮食(4.74克核苷酸/千克饮食),并在第3周和第6周用不完全弗氏佐剂(IFA)给予OVA(10微克/剂量)。我们通过分别测量Th1/Th2细胞因子、干扰素-γ(IFN-γ)和白细胞介素-5(IL-5)的产生和表达来评估局部引流淋巴结(LN)中的T细胞反应。在第一次OVA攻击后3周以及第二次OVA攻击后5天和2周测定抗OVA IgG亚类和IgE Ab水平。在第一次和第二次OVA攻击后,膳食核糖核苷酸显著增加了局部引流LN细胞产生的OVA特异性IFN-γ。NS饮食在第一次OVA攻击后增加了抗OVA IgG2a Ab水平,在第二次攻击后增加了抗OVA IgG2a和抗OVA IgG2b水平。在第二次OVA攻击后,喂食NS饮食的小鼠中OVA特异性IgG1和IgE Ab水平较低(P<0.05)。膳食核糖核苷酸不影响IL-5的产生或表达。因此,我们的研究结果表明,在Th2倾向的BALB/c J小鼠中,膳食核糖核苷酸通过产生Th1细胞因子IFN-γ和抗OVA Ab同种型水平的变化,将针对OVA的偏向一侧的Th2反应调节为Th1反应。