Regulatory T cells are expanded in blood and disease sites in patients with tuberculosis
Regulatory T cells are expanded in blood and disease sites in patients with tuberculosis
复制标题
DOI：
10.1164/rccm.200508-1294oc
复制
发表时间：
2006-04-01
影响因子：
24.7
通讯作者：
Lalvani, A
中科院分区：
文献类型：
--
作者：
Guyot-Revol, V;Innes, JA;Lalvani, A
理由：结核病 (TB) 期间的 T 细胞反应有助于抑制体内结核分枝杆菌，但也会对宿主组织造成附带损害。免疫调节机制可能会限制这种免疫病理学，结核病患者的细胞免疫反应受到抑制表明存在调节活性。 CD4+CD25（高）调节性 T 细胞在几种慢性感染中介导抑制的细胞免疫，但在结核病中尚未得到描述。目的：确定结核病患者中调节性 T 细胞是否增加以及它们是否抑制细胞免疫反应。方法：我们使用两种特定标记物：细胞表面 CD25 表达，比较了 27 名未经治疗的结核病患者和 23 名健康对照受试者中循环调节性 T 细胞的频率 测量和主要结果：我们检测到结核病患者中 CD4+CD25(高) T 细胞的频率增加了三倍 (p < 0.001)，FoxP3 表达增加了 2.2 倍 (p = 0.006)，并且这些标志物之间存在正相关性 (r = 0.58，p < 0.001)。在结核病患者中也检测到白细胞介素 10 和转化生长因子 01 mRNA 表达增加，但与调节性 T 细胞标记物无关。体外去除外周血单核细胞中的 CD4+CD25(high) 细胞导致 8 名结核病患者中的 7 名产生结核分枝杆菌抗原特异性 IFN-γ 的 T 细胞数量增加 (p = 0.005)。最后，与纯肺结核患者相比，肺外结核患者的 FoxP3 表达增加了 2.3 倍 (p = 0.01)，并且在疾病部位相对于血液扩增了 2.6 倍 (p = 0.043)。 结论：调节性 T 细胞在结核患者中扩增，可能有助于抑制 Th1 型免疫反应。
Rationale: T-cell responses during tuberculosis (TB) help contain Mycobacterium tuberculosis in vivo but also cause collateral damage to host tissues. Immune regulatory mechanisms may limit this immunopathology, and suppressed cellular immune responses in patients with TB suggest the presence of regulatory activity. CD4+CD25(high) regulatory T cells mediate suppressed cellular immunity in several chronic infections but have not been described in TB.Objective: To determine whether regulatory T cells are increased in patients with TB and whether they suppress cellular immune responses.Methods: We compared the frequency of circulating regulatory T cells in 27 untreated patients with TB and 23 healthy control subjects using two specific markers: cell-surface CD25 expression and FoxF3 mRNA expression in peripheral blood mononuclear cells.Measurements and Main Results: We detected a threefold increase in the frequency of CD4+CD25(high) T cells (p < 0.001) and a 2.2-fold increase in FoxP3 expression (p = 0.006) in patients with TB, and there was a positive correlation between these markers (r = 0.58, p < 0.001). Increased expression of interleukin-10 and transforming growth factor-01 mRNA was also detected in patients with TB but did not correlate with regulatory T-cell markers. Ex vivo depletion of CD4+CD25(high) cells from peripheral blood mononuclear cells resulted in increased numbers of M. tuberculosis antigen-specific IFN-y-producing T cells in seven of eight patients with TB (p = 0.005). Finally, FoxP3 expression was increased 2.3-fold in patients with extrapulmonary TB compared with patients with purely pulmonary TB (p = 0.01) and was amplified 2.6-fold at disease sites relative to blood (p = 0.043).Conclusions: Regulatory T cells are expanded in patients with TB and may contribute to suppression of Th1-type immune responses.