Manipulation and potentiation of antimycobacterial immunity using recombinant bacille Calmette-Guérin strains that secrete cytokines.
Manipulation and potentiation of antimycobacterial immunity using recombinant bacille Calmette-Guérin strains that secrete cytokines.
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DOI：
10.1073/pnas.93.2.934
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发表时间：
1996-01
影响因子：
11.1
通讯作者：
Peter J. Murray;A. Aldovini;Richard A. Young
中科院分区：
文献类型：
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作者：
Peter J. Murray;A. Aldovini;Richard A. Young
卡介苗（Bacille Calmette-Guérin，BCG）是一种牛分枝杆菌减毒活菌株，广泛用于结核病预防和膀胱癌免疫治疗，尽管它在这两种情况下都有局限性。为了研究BCG的免疫刺激特性是否可以被修改，并深入了解分枝杆菌和它们的宿主之间的相互作用，我们构建了分泌功能性鼠细胞因子的重组BCG菌株，并在实验感染的小鼠模型中研究了它们的特性。使用接种各种BCG重组体的小鼠的脾细胞测定对分枝杆菌抗原（纯化蛋白衍生物）的细胞介导的免疫应答。抗原特异性增殖和细胞因子的释放被发现是实质上更大的脾细胞来自小鼠注射的分泌精氨酸的BCG比脾细胞来自小鼠注射的BCG缺乏细胞因子。最深刻的影响是由BCG分泌的白细胞介素2，干扰素γ，或粒细胞-巨噬细胞集落刺激因子诱导的。因此，分泌马槟榔碱的BCG可以增强对分枝杆菌抗原的免疫应答，并且可以改进用于结核病预防和癌症免疫治疗的试剂。
Bacille Calmette-Guérin (BCG) is a live, attenuated strain of Mycobacterium bovis used widely for tuberculosis prophylaxis and bladder cancer immunotherapy, although it has limitations in both contexts. To investigate whether BCG's immunostimulatory properties could be modified, and to gain insight into the interaction between mycobacteria and their hosts, we constructed recombinant BCG strains that secrete functional murine cytokines and studied their properties in mouse models of experimental infection. Cell-mediated immune responses to mycobacterial antigen (purified protein derivative) were assayed using splenocytes from mice inoculated with various BCG recombinants. Antigen-specific proliferation and cytokine release were found to be substantially greater with splenocytes derived from mice injected with cytokine-secreting BCG than with splenocytes from mice injected with BCG lacking cytokines. The most profound effects were induced by BCG secreting interleukin 2, interferon gamma, or granulocyte-macrophage colony-stimulating factor. Thus, cytokine-secreting BCG can enhance immune responses to mycobacterial antigens and may be improved reagents for tuberculosis prophylaxis and cancer immunotherapy.