CD4+ T cell clones producing both interferon-γ and interleukin-10 predominate in bronchoalveolar lavages of active pulmonary tuberculosis patients
CD4+ T cell clones producing both interferon-γ and interleukin-10 predominate in bronchoalveolar lavages of active pulmonary tuberculosis patients
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DOI：
10.1006/clim.1999.4752
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发表时间：
1999-09-01
影响因子：
8.6
通讯作者：
Trinchieri, G
中科院分区：
文献类型：
--
作者：
Gerosa, F;Nisii, C;Trinchieri, G
分析了活动性肺结核(TB)患者支气管肺泡灌洗液(BAL)中T细胞克隆的细胞因子产生模式，这些克隆是通过限制稀释程序获得的克隆，这些克隆可以高效地扩增总T淋巴细胞，而不依赖于它们的抗原识别特异性，或者是结核分枝杆菌特异性T细胞。来自5名活动性结核病患者的代表CD4(+)细胞的BAL来源的克隆产生的TFN-γ显著高于来自3名非活动性结核病捐献者或4名对照(无相关、非感染性病理)的BAL来源的CD4(+)克隆。IL-4和IL-10的平均产量在三组间无显著差异。尽管这些数据表明肺脏对结核分枝杆菌感染的Th1反应占主导地位，但大多数BAL来源的CD4(+)克隆同时产生干扰素-γ和IL-10，而且在活动性结核病患者的BAL来源的克隆中，具有这种细胞因子产生模式的克隆的百分比显著高于对照组。只有来自患者(9例)和对照组(4例)外周血CD45RO(+)CD4(+)T细胞的罕见克隆同时产生干扰素-γ和IL-10；相反，产生IL-10的克隆来自。外周血T细胞也最常产生IL-4，表现为典型的Th2表型。4例活动性肺结核患者BAL来源的CD8(+)克隆产生LFN-γ和IL-10的平均水平高于4例对照，但CD8(+)克隆同时产生TFN-γ和IL-10的频率低于CD4(+)克隆。来自三名活动性结核病患者的结核分枝杆菌特异性BAL来源的T细胞克隆几乎完全是CD4(+)，并产生持续高水平的干扰素-γ，通常与IL-10有关，但很少与IL-4相关。与BAL来源的克隆不同，来自三名不同活动性结核病患者和两名健康献血者外周血CD45RO+CD4+T细胞的结核分枝杆菌特异性克隆在细胞因子产生以及CD4(+)、CD8(+)或TCRγ/Delta(+)克隆的比例上显示出很大的个体差异。这些结果表明，活动性肺结核患者BAL中以CD4(+)T细胞同时产生促炎细胞因子干扰素-γ和抗炎细胞因子IL-10为主。(C)1999年学术出版社。
The pattern of cytokine production in T cell clones derived from bronchoalveolar lavages (BAL) of active pulmonary tuberculosis (TB) patients was analyzed in clones obtained by limiting dilution procedures which expand with high efficiency either total T lymphocytes, independently of their antigen-recognition specificity, or Mycobacterium tuberculosis-specific T cells. BAL-derived clones, representative of CD4(+) cells from five patients with active TB, produced significantly higher amounts of TFN-gamma than BAL-derived CD4(+) clones from three inactive TB donors or four controls (with unrelated, noninfectious pathology). Average IL-4 and IL-10 production did not differ significantly in the three groups. Although these data suggest a predominant Th1 response to M; tuberculosis infection in the lungs, the majority of BAL-derived CD4(+) clones produced both IFN-gamma and IL-10 and the percentage of clones with this pattern of cytokine production was significantly higher in clones derived from BAL of active TB patients than from controls. Only rare clones derived from peripheral blood (PB)derived CD45RO(+) CD4(+) T cells of both patients (nine cases) and controls (four cases) produced both IFN-gamma and IL-10; instead, the IL-10-producing clones derived from. PB T cells most often also produced IL-4, displaying a typical Th2 phenotype. Higher average amounts of lFN-gamma and IL-10 were produced by BAL-derived CD8(+) clones of four active TB patients than of four controls, although the frequency of CD8(+) clones producing both TFN-gamma and IL-10 was lower than that of CD4(+) clones. The M tuberculosis-specific BAL-derived T cell clones from three active TB patients were almost exclusively CD4(+) and produced consistently high levels of IFN-gamma often in association with IL-10, but very rarely with IL-4. Unlike the BAL-derived clones, the M. tuberculosis-specific clones derived from PB CD45RO+ CD4+ T cells of three different active TB patients and two healthy donors showed large individual variability in cytokine production as well as in the proportion of CD4(+), CD8(+), or TCR gamma/delta(+) clones. These results indicate the predominance of CD4(+) T cells producing both the proinflammatory cytokine IFN-gamma and the anti-inflammatory cytokine IL-10 in BAL of patients with active TB. (C) 1999 Academic Press.