Modulation of naive CD4+ T-cell responses to an airway antigen during pulmonary mycobacterial infection
Modulation of naive CD4+ T-cell responses to an airway antigen during pulmonary mycobacterial infection
复制标题
DOI：
10.1128/iai.01709-06
复制
发表时间：
2007-05-01
影响因子：
3.1
通讯作者：
Boom, W. Henry
中科院分区：
文献类型：
--
作者：
Anis, Mursalin M.;Fulton, Scott A.;Boom, W. Henry
在肺部分枝杆菌感染期间，树突状细胞从肺部到引流淋巴结的运输增加。我们假设持续的分枝杆菌感染会在气道抗原攻击后调节抗原特异性初始 CD4(+) T 细胞的募集和激活。 BALB/c 小鼠通过含有牛分枝杆菌 BCG 的气溶胶感染。在肺部细菌负荷达到峰值时（感染后 4 至 6 周），将羧基荧光素二乙酸酯琥珀酰亚胺酯标记的幼稚卵清蛋白特异性 DO11.10 T 细胞过继转移至感染和未感染的小鼠体内。受体小鼠接受可溶性卵清蛋白 (OVA) 鼻内攻击，并在肺、引流纵隔淋巴结 (MLN) 和脾脏中测量 OVA 特异性 T 细胞反应。 OVA 攻击导致感染和未感染小鼠引流 MLN 中 OVA 特异性 T 细胞的激活和增殖增加。然而，只有感染 BCG 的小鼠肺部具有显着的 OVA 特异性 T 细胞激活、增殖和 Th1 分化。 BCG感染导致气道OVA更多地分布到肺树突状细胞，并增强肺CD11c(+)细胞对OVA肽的呈递。总之，这些数据表明，现有的肺部分枝杆菌感染改变了肺树突状细胞的表型，使其能够激活肺部的抗原特异性幼稚 CD4(+) T 细胞，以响应气道抗原的攻击。
During pulmonary mycobacterial infection, there is increased trafficking of dendritic cells from the lungs to the draining lymph nodes. We hypothesized that ongoing mycobacterial infection would modulate recruitment and activation of antigen-specific naive CD4(+) T cells after airway antigen challenge. BALB/c mice were infected by aerosol with Mycobacterium bovis BCG. At peak bacterial burden in the lungs (4 to 6 weeks postinfection), carboxy-fluorescein diacetate succinimidyl ester-labeled naive ovalbumin-specific DO11.10 T cells were adoptively transferred into infected and uninfected mice. Recipient mice were challenged intranasally with soluble ovalbumin (OVA), and OVA-specific T-cell responses were measured in the lungs, draining mediastinal lymph nodes (MLN), and spleens. OVA challenge resulted in increased activation and proliferation of OVA-specific T cells in the draining MLN of both infected and uninfected mice. However, only BCG-infected mice had prominent OVA-specific T-cell activation, proliferation, and Th1 differentiation in the lungs. BCG infection caused greater distribution of airway OVA to pulmonary dendritic cells and enhanced presentation of OVA peptide by lung CD11c(+) cells. Together, these data suggest that an existing pulmonary mycobacterial infection alters the phenotype of lung dendritic cells so that they can activate antigen-specific naive CD4(+) T cells in the lungs in response to airway antigen challenge.