Control of Chronic Mycobacterium tuberculosis Infection by CD4 KLRG1- IL-2-Secreting Central Memory Cells
Control of Chronic Mycobacterium tuberculosis Infection by CD4 KLRG1- IL-2-Secreting Central Memory Cells
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DOI：
10.4049/jimmunol.1300248
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发表时间：
2013-06-15
影响因子：
4.4
通讯作者：
Andersen, Peter
中科院分区：
文献类型：
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作者：
Lindenstrom, Thomas;Knudsen, Niels Peter Hell;Andersen, Peter
卡介苗在结核分枝杆菌攻击的标准动物模型中提供非常有效的保护。本文表明，虽然卡介苗控制了M。结核菌感染7周后，随着感染进入慢性期，保护作用逐渐丧失。M.结核病与产生IL-2的CD 4 T细胞几乎完全消失一致。用亚单位疫苗（Ag 85 B-ESAT-6+ CAF 01）加强接种可扩增共表达TNF-α或TNF-α/IFN-γ的IL-2（+）CD 4（+）T细胞，并且在感染后期维持该群体与增强的细菌生长控制相关。当动物在接种后2年进行攻毒时，IL-2（+）CD 4（+）T细胞亚群为KLRG 1（-）（非终末分化），发现CD 62 L高，并且在引流淋巴结中进一步保持了显著的增殖和产生精氨酸的潜力。这些结果表明，CD 4（+）KLRG 1（-）IL-2分泌亚群是中央记忆T细胞，具有持续补充感染部位T细胞并防止磨损和功能衰竭的潜力。
The bacille Calmette-Guerin vaccine provides very efficient protection in standard animal models of Mycobacterium tuberculosis challenge. We show in this article that although bacille Calmette-Guerin controlled M. tuberculosis growth for 7 wk of infection, the protection was gradually lost as the infection entered the chronic phase. The regrowth of M. tuberculosis coincided with an almost complete disappearance of IL-2-producing CD4 T cells. Booster vaccination with a subunit vaccine (Ag85B-ESAT-6+ CAF01) expanded IL-2(+) CD4(+) T cell coexpressing either TNF-alpha or TNF-alpha/IFN-gamma, and the maintenance of this population in the late stage of infection was associated with enhanced control of bacterial growth. The IL-2(+) CD4(+) T cell subsets were KLRG1(-) (nonterminally differentiated), were found to be CD62L high, and further maintained a pronounced proliferative and cytokine-producing potential in the draining lymph nodes, when the animals were challenged 2 y postvaccination. These results suggest that the CD4(+) KLRG1(-) IL-2-secreting subsets are central memory T cells with the potential to continuously replenish the T cells at the site of infection and prevent attrition and functional exhaustion.