Mannose-capped lipoarabinomannan- and prostaglandin E2-dependent expansion of regulatory T cells in human Mycobacterium tuberculosis infection
Mannose-capped lipoarabinomannan- and prostaglandin E2-dependent expansion of regulatory T cells in human Mycobacterium tuberculosis infection
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DOI：
10.1002/eji.200737268
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发表时间：
2008-02-01
影响因子：
5.4
通讯作者：
Vankayalapati, Ramakrishna
中科院分区：
文献类型：
--
作者：
Garg, Ankita;Barnes, Peter F.;Vankayalapati, Ramakrishna
我们评估了调节性T细胞（CD 4（+）CD 25（+）Foxp 3（+）细胞，TcB）在结核分枝杆菌感染中的作用。T细胞扩增反应M.结核病在健康的结核菌素反应者，但不是在结核菌素阴性的个人。分枝结核分枝杆菌甘露糖帽脂阿拉伯甘露聚糖（ManLAM）导致调节性T细胞扩增，而M.结核19-kDa蛋白和热休克蛋白65没有影响。单独或组合的抗IL-10和抗TGF-β不减少TcB的扩增。相比之下，环加氧酶-2抑制剂NS 398显著抑制Treg的扩增，表明前列腺素E2（PGE 2）有助于Treg扩增。单核细胞在与热灭活的M.来自健康结核菌素反应者的T细胞增强单核细胞的PGE 2产生。扩增的TGF-beta产生显著量的TGF-β和IL-10，并且从这些个体的PBMC中去除TGF-beta增加了M的频率。结核反应性CD 4（+）IFN-γ细胞。培养M.结核病用自体CD 8（+）细胞扩增的Treg降低了IFN-γ（+）细胞的频率。与健康的结核菌素反应者相比，从结核病患者新鲜分离的PBMC中THBE的百分比增加。这些结果表明，TcR响应于M.结核病通过依赖ManLAM和PGE 2的机制。
We evaluated the role of regulatory T cells (CD4(+) CD25(+) Foxp3(+) cells, Tregs) inhuman Mycobacterium tuberculosis infection. Tregs were expanded in response to M. tuberculosis in healthy tuberculin reactors, but not in tuberculin-negative individuals. The M. tuberculosis mannose-capped lipoarabinomannan (ManLAM) resulted in regulatory T cell expansion, whereas the M. tuberculosis 19-kDa protein and heat shock protein 65 had no effect. Anti-IL-10 and anti-TGF-beta alone or in combination, did not reduce expansion of Tregs. In contrast, the cyclooxygenase enzyme-2 inhibitor NS398 significantly inhibited expansion of Tregs, indicating that prostaglandin E2 (PGE2) contributes to Treg expansion. Monocytes produced PGE2 upon culturing with heat-killed M. tuberculosis or ManLAM, and T cells from healthy tuberculin reactors enhanced PGE2 production by monocytes. Expanded Tregs produced significant amounts of TGF-beta and IL-10 and depletion of Tregs from PBMC of these individuals increased the frequency of M. tuberculosis-responsive CD4(+) IFN-gamma cells. Culturing M. tuberculosis -expanded Tregs with autologous CD8(+) cells decreased the frequency of IFN-gamma(+) cells. Freshly isolated PBMC from tuberculosis patients had increased percentages of Tregs, compared to healthy tuberculin reactors. These findings demonstrate that Tregs expand in response to M. tuberculosis through mechanisms that depend on ManLAM and PGE2.