Guyot-Revol Valerie, Innes John A, Hackforth Sarah, Hinks Tim, Lalvani Ajit
Tuberculosis Immunology Group, Nuffield Department of Medicine, University of Oxford, John Radcliffe Hospital, Level 7, Oxford OX3 9DU, UK.
Am J Respir Crit Care Med. 2006 Apr 1;173(7):803-10. doi: 10.1164/rccm.200508-1294OC. Epub 2005 Dec 9.
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.
To determine whether regulatory T cells are increased in patients with TB and whether they suppress cellular immune responses.
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 FoxP3 mRNA expression in peripheral blood mononuclear cells.
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-beta1 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-gamma-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).
Regulatory T cells are expanded in patients with TB and may contribute to suppression of Th1-type immune responses.
结核病（TB）期间的T细胞反应有助于在体内控制结核分枝杆菌，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反应，而结核病患者中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细胞免疫抑制，但在结核病中尚未见报道。
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。
我们使用两种特异性标志物，比较了27例未经治疗的结核病患者和23名健康对照者循环调节性T细胞的频率：外周血单个核细胞表面CD25表达和FoxP3 mRNA表达。
我们检测到结核病患者中CD4 + CD25（高）T细胞频率增加了三倍（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（r = 0.58，p < 0.001）。在结核病患者中还检测到白细胞介素-10和转化生长因子-β1 mRNA表达增加，但与调节性T细胞标志物无关。从外周血单个核细胞中体外去除CD4 + CD25（高）细胞导致8例结核病患者中的7例结核分枝杆菌抗原特异性产生干扰素-γ的T细胞数量增加（p = 0.005）。最后，与单纯肺结核患者相比，肺外结核患者的FoxP3表达增加了2.3倍（p = 0.01），并且相对于血液，疾病部位的FoxP3表达增加了2.6倍（p = 0.043）。
结核病患者中调节性T细胞扩增，可能有助于抑制Th1型免疫反应。
