Simultaneous Inhibition of T Helper 2 and T Regulatory Cell Differentiation by Small Molecules Enhances Bacillus Calmette-Guerin Vaccine Efficacy against Tuberculosis
Simultaneous Inhibition of T Helper 2 and T Regulatory Cell Differentiation by Small Molecules Enhances Bacillus Calmette-Guerin Vaccine Efficacy against Tuberculosis
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DOI：
10.1074/jbc.m114.600452
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发表时间：
2014-11-28
影响因子：
4.8
通讯作者：
Das, Gobardhan
中科院分区：
文献类型：
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作者：
Bhattacharya, Debapriya;Dwivedi, Ved Prakash;Das, Gobardhan
结核病影响着900万人，每年造成近200万人死亡。唯一可用的疫苗是卡介苗（BCG），自1921年问世以来一直在使用。虽然BCG诱导宿主保护性T辅助1（Th1）细胞免疫应答，其在宿主保护中起核心作用，但其功效不令人满意，这表明需要其他方法来增强保护性免疫应答。最近，我们已经表明，通过分别使用药理学抑制剂甲苯磺酸舒普司特和D4476同时抑制Th2细胞和TcB，显著增强结核分枝杆菌清除并诱导上级Th1应答。在这里，我们表明，在卡介苗接种期间使用这两种药物治疗可显著提高疫苗效力。此外，我们证明，这些药物诱导T细胞记忆的发展中的转变，有利于中央记忆T（Tcm）细胞反应效应记忆T（Tem）细胞反应。总的来说，我们的研究结果提供的证据表明，在BCG疫苗接种过程中同时抑制Th2细胞和TcB细胞可以促进疫苗的有效性。
Tuberculosis affects nine million individuals and kills almost two million people every year. The only vaccine available, Bacillus Calmette-Guerin (BCG), has been used since its inception in 1921. Although BCG induces host-protective T helper 1 (Th1) cell immune responses, which play a central role in host protection, its efficacy is unsatisfactory, suggesting that additional methods to enhance protective immune responses are needed. Recently we have shown that simultaneous inhibition of Th2 cells and Tregs by using the pharmacological inhibitors suplatast tosylate and D4476, respectively, dramatically enhances Mycobacterium tuberculosis clearance and induces superior Th1 responses. Here we show that treatment with these two drugs during BCG vaccination dramatically improves vaccine efficacy. Furthermore, we demonstrate that these drugs induce a shift in the development of T cell memory, favoring central memory T (Tcm) cell responses over effector memory T (Tem) cell responses. Collectively, our findings provide evidence that simultaneous inhibition of Th2 cells and Tregs during BCG vaccination promotes vaccine efficacy.