Murray P J, Aldovini A, Young R A
Whitehead Institute for Biomedical Research, Nine Cambridge Center, MA 02142, USA.
Proc Natl Acad Sci U S A. 1996 Jan 23;93(2):934-9. doi: 10.1073/pnas.93.2.934.
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.
卡介苗（BCG）是一种减毒活牛分枝杆菌菌株，广泛用于结核病预防和膀胱癌免疫治疗，尽管在这两种情况下它都有局限性。为了研究卡介苗的免疫刺激特性是否可以被改变，并深入了解分枝杆菌与其宿主之间的相互作用，我们构建了分泌功能性小鼠细胞因子的重组卡介苗菌株，并在实验性感染的小鼠模型中研究了它们的特性。使用接种了各种卡介苗重组体的小鼠的脾细胞，检测对分枝杆菌抗原（纯化蛋白衍生物）的细胞介导免疫反应。发现注射分泌细胞因子的卡介苗的小鼠来源的脾细胞，其抗原特异性增殖和细胞因子释放比注射缺乏细胞因子的卡介苗的小鼠来源的脾细胞要显著得多。分泌白细胞介素2、干扰素γ或粒细胞-巨噬细胞集落刺激因子的卡介苗诱导的效果最为显著。因此，分泌细胞因子的卡介苗可以增强对分枝杆菌抗原的免疫反应，可能是用于结核病预防和癌症免疫治疗的改良试剂。
