Institute of Virology and Immunobiology, University of Würzburg, Würzburg, Germany.
BMC Immunol. 2013 Oct 3;14:48. doi: 10.1186/1471-2172-14-48.
Mycobacterium tuberculosis (Mtb) infections are still a major cause of death among all infectious diseases. Although 99% of individuals infected with Mtb develop a CD4(+) Th1 and CD8(+) T cell mediated immunity as measured by tuberculin skin test, this results only in partial protection and Mtb vaccines are not effective. Deviation of immune responses by pathogens towards a Th2 profile is a common mechanism of immune evasion, typically leading to the persistence of the microbes.
Here we tested the stimulatory capacity of selective Mtb antigens on human monocyte-derived dendritic cell (DC) maturation and cytokine production. DC maturation markers CD80, CD86 and CD83 were readily upregulated by H37Ra- and H37Rv-associated antigens, the 30-kDa (from Ag85 B complex) and 38-KDa Mtb antigens only partially induced these markers. All Mtb antigens induced variable levels of IL-6 and low levels of IL-10, there was no release of IL-12p70 detectable. Substantial IL-12p40 production was restricted to LPS or H37Ra and H37Rv preparations. Although the proliferation levels of primary T cell responses were comparable using all the differentially stimulated DC, the 30-kDa and 38-kDa antigens showed a bias towards IL-4 secretion of polarized CD4(+) T cells after secondary stimulation as compared to H37Ra and H37Rv preparations.
Together our data indicate that 30-kDa and 38-kDa Mtb antigens induced only partial DC maturation shifting immune responses towards a Th2 profile.
结核分枝杆菌（Mtb）感染仍然是所有传染病中导致死亡的主要原因。尽管 99%的 Mtb 感染者通过结核菌素皮肤试验表现出 CD4(+) Th1 和 CD8(+) T 细胞介导的免疫，但这仅导致部分保护，并且 Mtb 疫苗无效。病原体将免疫反应向 Th2 表型偏离是免疫逃避的常见机制，通常导致微生物的持续存在。
在这里，我们测试了选择性 Mtb 抗原对人单核细胞衍生树突状细胞（DC）成熟和细胞因子产生的刺激能力。DC 成熟标志物 CD80、CD86 和 CD83 很容易被 H37Ra 和 H37Rv 相关抗原上调，而 30-kDa（来自 Ag85 B 复合物）和 38-KDa Mtb 抗原仅部分诱导这些标志物。所有 Mtb 抗原诱导可变水平的 IL-6 和低水平的 IL-10，没有检测到 IL-12p70 的释放。大量的 IL-12p40 产生仅限于 LPS 或 H37Ra 和 H37Rv 制剂。尽管使用所有差异刺激的 DC 均可检测到原代 T 细胞反应的增殖水平相当，但与 H37Ra 和 H37Rv 制剂相比，30-kDa 和 38-kDa Mtb 抗原在二次刺激后显示出向极化 CD4(+) T 细胞分泌 IL-4 的偏向性。
我们的数据表明，30-kDa 和 38-kDa Mtb 抗原仅诱导部分 DC 成熟，将免疫反应向 Th2 表型转移。
