Severe Reduction in Number and Function of Peripheral T Cells Does Not Afford Protection toward Emphysema and Bronchial Remodeling Induced in Mice by Cigarette Smoke
Severe Reduction in Number and Function of Peripheral T Cells Does Not Afford Protection toward Emphysema and Bronchial Remodeling Induced in Mice by Cigarette Smoke
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DOI：
10.1016/j.ajpath.2016.03.002
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发表时间：
2016-07-01
影响因子：
6
通讯作者：
Lucattelli, Monica
中科院分区：
文献类型：
--
作者：
De Cunto, Giovanna;Lunghi, Benedetta;Lucattelli, Monica
蛋白Lck（p56（Lck））是在胸腺细胞发育的所有阶段表达的Src家族酪氨酸激酶，并且是T细胞成熟所需的。小鼠Lck基因的靶向破坏导致胸腺细胞成熟严重受阻，CD 4（+）CD 8（+）胸腺细胞发育显著减少，外周T细胞严重减少，T细胞受体信号传导中断，T细胞应答功能缺陷。为探讨T淋巴细胞在香烟烟雾致肺损伤中的作用，采用Lck（-/-）小鼠和相应的野生型小鼠慢性香烟烟雾暴露，并对其肺进行生化、免疫学和形态计量学分析。两种基因型的吸烟小鼠均表现出肺气肿的播散灶和支气管和细支气管上皮中大面积的杯状细胞化生。肺变化的形态学评估和肺弹性蛋白测定证实，两种基因型小鼠表现出相同程度的肺气肿病变。因此，在外周T细胞数量和功能严重减少的情况下，香烟烟雾暴露不会影响香烟烟雾诱导的肺变化的发展。获得的数据表明，先天免疫是吸烟小鼠肺部变化早期发展的主要因素，适应性免疫反应可能在后期发挥作用。
The protein Lck (p56(Lck)) is a Src family tyrosine kinase expressed at all stages of thymocyte development and is required for maturation of T cells. The targeted disruption of Lck gene in mice results in severe block in thymocyte maturation with substantial reduction in the development of CD4(+)CD8(+) thymocytes, severe reduction of peripheral T cells, and disruption of T-cell receptor signaling with defective function of T-cell responses. To investigate the role of T lymphocyte in the development of cigarette smoke induced pulmonary changes, Lck(-/-) mice and corresponding congenic wild-type mice were chronically exposed to cigarette smoke, and their lungs were analyzed by biochemical, immunologic, and morphometric methods. Smoking mice from both genotypes showed disseminated foci of emphysema and large areas of goblet cell metaplasia in bronchial and bronchiolar epithelium. Morphometric evaluation of lung changes and lung elastin determination confirmed that mice from both genotypes showed the same degree of emphysematous lesions. Thus, cigarette smoke exposure in the presence of severe reduction in number and function of peripheral T cells does not influence the development of pulmonary changes induced by cigarette smoke. The data obtained suggest that innate immunity is a leading actor in the early development of pulmonary changes in smoking mice and that the adaptive immune response may play a role at later stages.