Impact of inducible co-stimulatory molecule (ICOS) on T-cell responses and protection against Mycobacterium tuberculosis infection
Impact of inducible co-stimulatory molecule (ICOS) on T-cell responses and protection against Mycobacterium tuberculosis infection
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DOI：
10.1002/eji.201040608
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发表时间：
2011-04-01
影响因子：
5.4
通讯作者：
Kaufmann, Stefan H. E.
中科院分区：
文献类型：
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作者：
Nouailles, Geraldine;Day, Tracey A.;Kaufmann, Stefan H. E.
尽管结核分枝杆菌（Mtb）仍然是最大的微生物杀手之一，但在20亿感染者中，超过90%的人从未发展为活动性结核病（TB），这表明这些人的感染得到了有效的免疫控制。促进结核病控制或再激活的免疫机制尚不完全清楚。对C57BL/6小鼠抗结核T细胞反应的动力学分析显示，诱导共刺激分子（ICOS）在约30%的CD4(+) T细胞表面表达，表明这种CD28家族的共刺激分子在结核控制中起关键作用。令人惊讶的是，与WT对照组相比，mtb感染的ICOS /小鼠在感染的慢性晚期表现出较低的细菌负担。在晚期感染期间，ICOS缺乏导致mtb特异性CD8(+) t细胞反应降低。相比之下，多克隆CD4(+) Th1对Mtb的应答增加，很可能是由于Tregs的数量和频率减少所致。因此，通过不同地改变效应t细胞群，ICOS信号在感染后期调节结核病控制。
Even though Mycobacterium tuberculosis (Mtb) remains one of the top microbial killers, more than 90% of the 2 billion infected individuals never develop active tuberculosis (TB), indicating efficient immune control of infection in these individuals. Immune mechanisms promoting either control or reactivation of TB are incompletely understood. Kinetic analyses of T-cell responses against Mtb in C57BL/6 mice revealed surface expression of inducible co-stimulatory molecule (ICOS) on >30% of all CD4(+) T cells, suggesting a pivotal role of this costimulatory molecule of the CD28 family in TB control. Surprisingly, Mtb-infected ICOS / mice showed lower bacterial burden during the late chronic stage of infection as compared to WT controls. ICOS deficiency resulted in a reduced Mtb-specific CD8(+) T-cell response during late-stage infection. In contrast, the polyclonal CD4(+) Th1 response against Mtb was increased, most likely caused by diminished numbers and frequencies of Tregs. Thus, by altering effector T-cell populations differentially, ICOS signaling modulates TB control in the late stage of infection.