难治性肺结核患者PBMCs结核分枝杆菌特异性Th1细胞因子反应低下

目的研究难治性肺结核患者外周血单个核细胞（PBMCs）经结核分枝杆菌特异性抗原肽（ESAT-6，CFP．10）刺激后代表性Thl细胞因子IFN一叫、IL-2和TNF．d的表达特点及意义。方法纳入67例初治肺结核患者、28例难治性肺结核患者和25位结核分枝杆菌潜伏感染者，分离外周血单个核细胞（PBMCs），用ESAT-6，CFP-10肽库刺激PBMCs，采用FlowCytomix流式技术检测细胞培养液上清中细胞因子IFN-γ、IL-2和TNF-α的浓度。结果PBMCs经结核分枝杆菌特异性抗原肽刺激后，IFN-γ、IL-2和TNF-α均因刺激而升高，初治组的三个因子的水平均显著高于难治组和潜伏感染组（与难治组比较，Mann-WhitneyU值=119．0，282．5、339．5，P均〈0．01；与潜伏感染组比较，Mann-WhitneyU值=387．0，477．0、374．5，P=0．0002，0．0033、0．0001），难治组IFN-γ和IL-2的水平显著低于潜伏感染组（Mann-WhitneyU值=105．5、162．5，P〈0．01），TNF-α的水平在难治组和潜伏感染组间的差异无统计学意义（Mann-WhitneyU值=265．0，P=0．2695）。结论难治性肺结核患者结核分枝杆菌特异性Thl细胞因子反应低下，针对结核病的免疫治疗可能对难治性肺结核发挥更大的作用。

Thl Cytokines induced by ESAT-6 and CFP-10 in PBMCs from patients with refractory pulmonarytuberculosis were impaired

Objective To investigate the feature of Thl cytokines induced by Mtb-specific antigen in patients with refractory pulmonary tuberculosis. Methods 28 patients with refractory pulmonary tubercu- losis, 67 patients with first-treated pulmonary tuberculosis, and 25 healthy controls with positive T. spot （LTBI group） were enrolled. IFN-γ, IL-2 and TNF-α in supernatants from PBMCs stimulated with ESAT-6 and CFP-10 were analyzed with Bender Flowcytomix on flow cytometry. Results The levels of the three cytokines were utmost high in patients with first-treated pulmonary tuberculosis. The lowest level of IFN-γand IL-2 were induced in patients with refractory pulmonary tuberculosis, and were significantly lower than the LTBI group（ Mann-Whitney U = 105.5,162. 5, P 〈 0.01 ）. Conclusions The immunotherapy with IFN-γ and IL-2 may play a role in treatment for refractory pulmonary tuberculosis but not for most of first-treated pulmonary tuberculosis.