Winkler Stefan, Necek Magdalena, Winkler Heidi, Adegnika Ayola A, Perkmann Thomas, Ramharter Michael, Kremsner Peter G
Department of Internal Medicine I, Division of Infectious Diseases, Medical University of Vienna, Waehringerguertel 18-20, 090 Vienna, Austria.
Microbes Infect. 2005 Jul;7(9-10):1161-9. doi: 10.1016/j.micinf.2005.03.020. Epub 2005 Apr 19.
An understanding of T cell responses that are crucial for control of Mycobacterium tuberculosis (MTB) has major implications for the development of immune-based interventions. We studied the frequency of purified protein derivative (PPD)-specific CD3) cells expressing interleukin-2 (IL)-2, gamma interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha and IL-10 in HIV-negative pulmonary tuberculosis patients (TB, n=30) as well as in healthy individuals (controls, n=21) from Central Africa. Increased frequencies of PPD-stimulated CD3+ cells expressing IL-2, IFN-gamma, and TNF-alpha in TB were seen when compared with frequencies of controls. The presence of type 1 cytokine biased responses in TB patients was supported by a shift in the distribution pattern of cytokine expression from exclusively IL-2 or TNF-alpha expression seen in controls towards an increased frequency of IFN-gamma/IL-2 or IFN-gamma/TNF-alpha co-expression in TB. Higher levels of PPD-induced IFN-gamma in the supernatants from TB patients than from controls were found, which correlated with its intracellular expression. PPD was a weak inducer of IL-10 in T cells and insufficient in promoting cytokine production in TCRgammadelta+CD3+ cells. Non-specific stimulation with PMA and ionomycin revealed increased frequencies of CD4+ cells expressing IFN-gamma in controls, while expression of IL-2, IL-4, IL-10, IL-13, and TNF-alpha was not different. Non-specific cytokine responses of TCRgammadelta+CD3+ cells were similar in all groups. Pulmonary TB in Central Africa is associated with enhanced expression and secretion of specifically induced cytokines that are frequently implicated in host defense against MTB.
了解对控制结核分枝杆菌（MTB）至关重要的T细胞反应对于基于免疫的干预措施的开发具有重要意义。我们研究了来自中非的HIV阴性肺结核患者（TB，n = 30）以及健康个体（对照组，n = 21）中表达白细胞介素-2（IL）-2、γ干扰素（IFN）-γ、肿瘤坏死因子（TNF）-α和IL-10的纯化蛋白衍生物（PPD）特异性CD3⁺细胞的频率。与对照组相比，TB患者中PPD刺激的表达IL-2、IFN-γ和TNF-α的CD3⁺细胞频率增加。TB患者中1型细胞因子偏向性反应的存在得到了细胞因子表达分布模式变化的支持，即从对照组中仅见的IL-2或TNF-α表达转变为TB中IFN-γ/IL-2或IFN-γ/TNF-α共表达频率增加。发现TB患者上清液中PPD诱导的IFN-γ水平高于对照组，这与其细胞内表达相关。PPD是T细胞中IL-10的弱诱导剂，在促进TCRγδ⁺CD3⁺细胞中的细胞因子产生方面不足。用佛波酯（PMA）和离子霉素进行非特异性刺激显示，对照组中表达IFN-γ的CD4⁺细胞频率增加，而IL-2、IL-4、IL-10、IL-13和TNF-α的表达没有差异。所有组中TCRγδ⁺CD3⁺细胞的非特异性细胞因子反应相似。中非的肺结核与特异性诱导的细胞因子的表达和分泌增强有关，这些细胞因子经常参与宿主对MTB的防御。
