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首页> 外文期刊>Infection and immunity >Induction of cytotoxic T-cell responses against culture filtrate antigens in Mycobacterium bovis bacillus Calmette-Guérin-infected mice.
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Induction of cytotoxic T-cell responses against culture filtrate antigens in Mycobacterium bovis bacillus Calmette-Guérin-infected mice.

机译:在牛分枝杆菌卡门特-盖林感染的小鼠中诱导针对培养滤液抗原的细胞毒性T细胞反应。

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CD8+ T cells are essential for protection against mycobacteria, as is clearly demonstrated by the fatal outcome of experimental infection of beta-2 microglobulin knockout mice. However, the mechanisms and antigens (Ags) leading to CD8+ T-cell activation and regulation have been poorly characterized. Here we show that, upon immunization of major histocompatibility complex (MHC)-congenic mice with Mycobacterium bovis bacillus Calmette-Guérin (BCG), a cytotoxic response against BCG culture filtrate (CF) Ags (CFAgs) is induced in H-2b and H-2bxd haplotypes but not in H-2d haplotype. This response is mediated by CD8+ T cells and absolutely requires the activation of CD4+ T cells and their secretion of interleukin 2. The lack of cytotoxic response in H-2d mice cannot be explained by impaired cytokine production or by a defect in Ag presentation by H-2d macrophages. Using the MHC class I mutant B6.C-H-2bm13 mouse strain, we demonstrate that cytotoxic T lymphocytes (CTLs) recognize CFAgs exclusively in association with D(b) molecules. These Ags are cross-reactive in mycobacteria, since BCG-induced CTLs also recognize macrophages pulsed with CF from Mycobacterium tuberculosis H37Rv and H37Ra and from two virulent strains of M. bovis. Moreover, immunization with Mycobacterium kansasii induces CTLs able to lyse macrophages pulsed with BCG CF. Finally, we have found that these Ags can be characterized as hydrophilic proteins, since they do not bind to phenyl-Sepharose CL-4B. Our results indicate that MHC-linked genes exert a profound influence on the generation of CD8+ CTLs following BCG vaccination.
机译:CD8 + T细胞对于预防分枝杆菌至关重要,正如β-2微球蛋白敲除小鼠实验性感染的致命结果所清楚表明的那样。但是,导致CD8 + T细胞活化和调节的机制和抗原(Ags)的表征较差。在这里,我们显示,在用牛分枝杆菌卡介苗(BCG)免疫主要组织相容性复合体(MHC)基因的小鼠后,在H-2b和H中诱导了针对BCG培养滤液(CF)Ags(CFAgs)的细胞毒性反应。 -2bxd单倍型,但不是H-2d单倍型。这种反应是由CD8 + T细胞介导的,绝对需要激活CD4 + T细胞及其白介素2的分泌。H-2d小鼠缺乏细胞毒性反应,不能通过细胞因子生成受损或H的Ag呈递缺陷来解释。 -2d巨噬细胞。使用MHC I类突变体B6.C-H-2bm13小鼠品系,我们证明细胞毒性T淋巴细胞(CTL)仅与D(b)分子结合识别CFAg。这些抗原在分枝杆菌中具有交叉反应性,因为BCG诱导的CTL还可以识别来自结核分枝杆菌H37Rv和H37Ra以及来自牛分枝杆菌的两个强毒株的CF脉冲的巨噬细胞。此外,用堪萨斯分枝杆菌免疫可诱导CTLs裂解含BCG CF脉冲的巨噬细胞。最后,我们发现这些Ags可以表征为亲水蛋白,因为它们不与苯基-Sepharose CL-4B结合。我们的结果表明,在BCG疫苗接种后,与MHC相关的基因对CD8 + CTL的产生产生了深远的影响。

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