Koski Gary K, Karikó Katalin, Xu Shuwen, Weissman Drew, Cohen Peter A, Czerniecki Brian J
Harrison Department of Surgical Research, Department of Surgery, University of Pennsylvania, Philadelphia, PA 19104, USA.
J Immunol. 2004 Apr 1;172(7):3989-93. doi: 10.4049/jimmunol.172.7.3989.
RNA derived from bacterial but not eukaryotic sources, when transfected into human monocyte-derived dendritic cell precursors, induces high-level IL-12 secretion in conjunction with dendritic cell maturation stimuli. In vitro-transcribed mRNA that mimics the structure of bacterial mRNA in the lack of a long 3'-poly(A) tail likewise induces IL-12 secretion, but this property is lost upon efficient enzymatic 3'-polyadenylation. Among other tested RNAs, only polyuridylic acid induced IL-12 p70. This RNA response phenomenon appears biologically distinct from the classically defined response to dsRNA. RNA-transfected APC also polarize T cells in an IL-12-dependent manner toward the IFN-gamma(high)IL-5 (low) Th1 phenotype, suggesting a link between the detection of appropriately structured RNA and the skewing of immune responses toward those best suited for controlling intracellular microbes. RNA structured to emulate bacterial patterns constitutes a novel vaccine strategy to engender polarized Th1-type immune responses.
源自细菌而非真核生物的RNA，转染到人单核细胞衍生的树突状细胞前体中时，与树突状细胞成熟刺激物一起诱导高水平的IL-12分泌。在缺乏长3'-聚腺苷酸尾的情况下模拟细菌mRNA结构的体外转录mRNA同样诱导IL-12分泌，但这种特性在有效的酶促3'-聚腺苷酸化后丧失。在其他测试的RNA中，只有聚尿苷酸诱导IL-12 p70。这种RNA反应现象在生物学上似乎与经典定义的对双链RNA的反应不同。RNA转染的抗原呈递细胞也以IL-12依赖的方式将T细胞极化为IFN-γ（高）IL-5（低）Th1表型，这表明检测到适当结构的RNA与免疫反应偏向于最适合控制细胞内微生物的反应之间存在联系。构建成模拟细菌模式的RNA构成了一种产生极化Th1型免疫反应的新型疫苗策略。
