Hartl Dominik, Griese Matthias, Kappler Matthias, Zissel Gernot, Reinhardt Dietrich, Rebhan Christian, Schendel Dolores J, Krauss-Etschmann Susanne
Children's Hospital of the Ludwig-Maximilians-University of Munich, Munich, Germany.
J Allergy Clin Immunol. 2006 Jan;117(1):204-11. doi: 10.1016/j.jaci.2005.09.023. Epub 2005 Nov 28.
Pseudomonas aeruginosa infection determines the course of cystic fibrosis (CF) lung disease. Studies in human peripheral blood indicate that P aeruginosa infection is associated with a predominant T(H)2 immune response, whereas T(H)1 responses are accompanied by a better pulmonary outcome.
Analyses of peripheral blood may not correspond directly with the local pulmonary immune response. Therefore, we asked whether the T(H)1/T(H)2 response is altered in bronchoalveolar lavage fluid from P aeruginosa-infected patients with CF.
Bronchoalveolar lavage fluid was obtained from 12 patients with CF chronically infected with P aeruginosa, 11 noninfected patients with CF, and 8 healthy controls. Pulmonary CXCR3(+) (T(H)1) and CCR4(+) (T(H)2) expressing CD4(+) and CD8(+) lymphocytes were quantified by flow cytometry. Levels of T(H)1-associated (IL-2, IFN-gamma, IFN-gamma inducible T cell-alpha chemoattractant, Monokine induced by IFN-gamma, IFN-gamma inducible protein of 10 kd) and T(H)2-associated (IL-4, IL-5, IL-10, thymus and activation-regulated chemokine [TARC], macrophage-derived chemokine) cytokines and chemokines and a panel of proinflammatory molecules were quantified at the protein level. Chemokines mRNA levels were assessed by real time RT-PCR.
P aeruginosa-infected patients with CF had significantly higher levels of pulmonary CCR4(+)CD4(+) (T(H)2) cells, IL-4, IL-13, and TARC and lower levels of IFN-gamma compared with noninfected patients with CF and healthy controls. Bronchoalveolar lavage fluid levels of IL-4, IL-13, and TARC correlated inversely with FEV(1) in P aeruginosa-infected patients with CF.
These results reveal the prevalence of a pulmonary T(H)2 immune response in P aeruginosa-infected patients with CF. The modulation of the pulmonary T(H)2 response in P aeruginosa infection may be an option for the treatment of P aeruginosa lung disease in patients with CF.
铜绿假单胞菌感染决定了囊性纤维化（CF）肺部疾病的病程。对人体外周血的研究表明，铜绿假单胞菌感染与主要的T（H）2免疫反应相关，而T（H）1反应则伴随着较好的肺部预后。
对外周血的分析可能与局部肺部免疫反应并不直接对应。因此，我们探讨了在感染铜绿假单胞菌的CF患者的支气管肺泡灌洗液中，T（H）1/T（H）2反应是否发生改变。
从12例长期感染铜绿假单胞菌的CF患者、11例未感染的CF患者和8名健康对照者获取支气管肺泡灌洗液。通过流式细胞术对表达CXCR3（+）（T（H）1）和CCR4（+）（T（H）2）的肺CD4（+）和CD 8（+）淋巴细胞进行定量分析。在蛋白水平对与T（H）1相关的（白细胞介素-2、干扰素-γ、干扰素-γ诱导的T细胞α趋化因子、干扰素-γ诱导的单核因子、10kd的干扰素-γ诱导蛋白）和与T（H）2相关的（白细胞介素-4、白细胞介素-5、白细胞介素-10、胸腺和活化调节趋化因子[TARC]、巨噬细胞衍生趋化因子）细胞因子、趋化因子以及一组促炎分子进行定量分析。通过实时逆转录聚合酶链反应评估趋化因子mRNA水平。
与未感染的CF患者和健康对照者相比，感染铜绿假单胞菌的CF患者肺部CCR4（+）CD4（+）（T（H）2）细胞、白细胞介素-4、白细胞介素-13和TARC水平显著更高，而干扰素-γ水平更低。在感染铜绿假单胞菌的CF患者中，支气管肺泡灌洗液中白细胞介素-4、白细胞介素-13和TARC水平与第一秒用力呼气量呈负相关。
这些结果揭示了在感染铜绿假单胞菌的CF患者中肺部T（H）2免疫反应的普遍性。调节铜绿假单胞菌感染中的肺部T（H）2反应可能是治疗CF患者铜绿假单胞菌肺部疾病的一种选择。
