首页> 外文期刊>Molecular Immunology >Molecular differences between the divergent responses of ovalbumin-specific CD4 T cells to alum-precipitated ovalbumin compared to ovalbumin expressed by Salmonella.
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Molecular differences between the divergent responses of ovalbumin-specific CD4 T cells to alum-precipitated ovalbumin compared to ovalbumin expressed by Salmonella.

机译:与沙门氏菌表达的卵清蛋白相比,卵清蛋白特异性CD4 T细胞对明矾沉淀的卵清蛋白发散反应之间的分子差异。

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CD4 T helper (Th) cell differentiation defined by in vitro cytokine-directed culture systems leaves major gaps in our knowledge of the mechanisms driving divergent Th differentiation. This is evident from our analysis of the response of mouse ovalbumin-specific CD4 T cells to different forms of ovalbumin that induce markedly distinct responses in vivo. We show that live attenuated ovalbumin-expressing Salmonella (SalOVA) induce Th1-associated T-bet and IFN-gamma. Conversely, alum-precipitated ovalbumin (alumOVA) induces the Th2-associated GATA-3 and IL-4. The early diversity occurring within these CD4 T cells isolated 3 days after immunization was assessed using real-time RT-PCR microfluidic cards designed with 384 selected genes. The technique was validated both at the population and single cell levels at different stages of the responses, showing beta2-microglobulin to be a more stably expressed reference mRNA than either beta-actin or 18S RNA. SalOVA was then shown selectively to induce the OVA-specific CD4 T cells to produce many chemokines and pro-inflammatory cytokines, contrasting with alumOVA-induced cells that only produced a few Th2-associated cytokines. Several cytokines and features associated with follicular helper functions were induced in the OVA-specific CD4 T cells by both antigens. Finally, IL-17RB is strongly associated with OVA-specific CD4 T cells responding to alumOVA, suggesting that alum may promote Th2 immune response through a role for the IL-25/IL-17RB pathway.
机译:由体外细胞因子定向培养系统定义的CD4 T辅助(Th)细胞分化在我们了解不同Th分化机制的知识上存在重大差距。从我们对小鼠卵清蛋白特异性CD4 T细胞对不同形式卵清蛋白的反应的分析中可以明显看出,这些卵清蛋白在体内可诱导明显不同的反应。我们表明,活的减毒的表达卵白蛋白的沙门氏菌(SalOVA)诱导Th1相关的T-bet和IFN-γ。相反,明矾沉淀的卵清蛋白(alumOVA)诱导Th2相关的GATA-3和IL-4。使用设计有384个选定基因的实时RT-PCR微流卡评估了免疫3天后分离出的这些CD4 T细胞内发生的早期多样性。该技术在反应的不同阶段在群体水平和单细胞水平上均得到验证,表明β2-微球蛋白是比β-肌动蛋白或18S RNA更稳定表达的参考mRNA。然后显示SalOVA有选择地诱导OVA特异性CD4 T细胞产生许多趋化因子和促炎性细胞因子,而alumOVA诱导的细胞仅产生一些与Th2相关的细胞因子。两种抗原均在OVA特异性CD4 T细胞中诱导了几种与卵泡辅助功能相关的细胞因子和特征。最后,IL-17RB与应答于alumOVA的OVA特异性CD4 T细胞密切相关,这表明明矾可能通过IL-25 / IL-17RB途径的作用促进Th2免疫应答。

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