CD28 and CTLA4 coordinately regulate airway inflammatory cell recruitment and T-Helper cell differentiation after inhaled allergen
CD28 and CTLA4 coordinately regulate airway inflammatory cell recruitment and T-Helper cell differentiation after inhaled allergen
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DOI：
10.1165/ajrcmb.24.5.4375
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发表时间：
2001-05-01
影响因子：
6.4
通讯作者：
Green, JM
中科院分区：
文献类型：
--
作者：
Burr, JS;Kimzey, SL;Green, JM
吸入过敏原暴露后的气道炎症需要抗原特异性T细胞的募集、激活和分化为T辅助（Th） 2效应细胞。这些过程不仅受T细胞受体抗原结合的调节，还受T细胞表面特定辅助分子的调节。在小鼠过敏性气道炎症模型中，我们研究了CD28和细胞毒性t淋巴细胞抗原（CTLA） 4受体产生的信号平衡如何调节吸入抗原暴露的结果。缺乏CD28的小鼠Th2细胞发育有缺陷，在致敏和吸入卵清蛋白后不能发生炎症。预防B7-CTLA4在cd28缺陷小鼠中的相互作用可以恢复淋巴细胞，但不能恢复气道嗜酸性粒细胞的募集。细胞因子基因表达分析显示，cd28缺陷小鼠的T细胞在存在或不存在b7依赖信号的情况下都不能分化为Th2细胞，因此不能向气道招募嗜酸性粒细胞。因此，t细胞向气道募集和t细胞分化的过程对CD28和CTLA4受体介导的信号有不同的要求，表明这些受体是过敏性气道炎症发展的重要调节成分。
Airway inflammation after inhaled allergen exposure requires the recruitment, activation, and differentiation of antigen-specific T cells into T helper (Th) 2 effector cells. These processes are regulated not only by antigen engagement of the T-cell receptor, but also by specific accessory molecules on the surface of the T cell. We examined how the balance of signals derived through the CD28 and cytotoxic T-lymphocyte antigen (CTLA) 4 receptors modulate the outcome of inhaled antigen exposure in a murine model of allergic airway inflammation. Mice deficient in CD28 have defective Th2 cell development and failed to develop inflammation after sensitization and inhaled challenge with ovalbumin. Prevention of B7-CTLA4 interactions in CD28-deficient mice restored lymphocyte but not eosinophil recruitment to the airway. Analysis of cytokine gene expression revealed that T cells from CD28-deficient mice failed to differentiate into Th2 cells in either the presence or absence of B7-dependent signals, and therefore did not recruit eosinophils to the airway. Thus, the processes of T-cell recruitment to the airway and T-cell differentiation have distinct requirements for signals mediated through the CD28 and CTLA4 receptors, demonstrating that these receptors are important regulatory components in the development of allergic airway inflammation.