CD8+ T cell-mediated airway hyperresponsiveness and inflammation is dependent on CD4+IL-4+ T cells
CD8+ T cell-mediated airway hyperresponsiveness and inflammation is dependent on CD4+IL-4+ T cells
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DOI：
10.4049/jimmunol.179.5.2787
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发表时间：
2007-09-01
影响因子：
4.4
通讯作者：
Gelfand, Erwin W.
中科院分区：
文献类型：
--
作者：
Koya, Toshiyuki;Miyahara, Nobuaki;Gelfand, Erwin W.
CD 4（+）T细胞，特别是Th 2细胞，在过敏性气道炎症中起关键作用。然而，在气道变应性炎症中CD 4+和CD 8（+）T细胞之间相互作用的要求尚未阐明。致敏和激发的OT-1小鼠中，表达OVA（257-264）肽（SIINFEKL）转基因的CD 8（+）T细胞未发生气道高反应性（AHR）、气道嗜酸性粒细胞增多、Th 2细胞因子升高或杯状细胞化生。在致敏前接受初始CD 4（+）IL-4（+）T细胞但不接受CD 4（+）IL-4（-）T细胞的OT-1小鼠产生了与野生型小鼠相同程度的所有这些反应。此外，CD 4（+）IL-4（+）T细胞的接受者肺部CD 8（+）IL-13（+）T细胞的数量显着增加，而在激发前接受致敏CD 4（+）T细胞的致敏OT-1小鼠未能产生这些反应。在致敏前接受初始CD 4（+）T细胞的OT-1小鼠中接受CD 8（+）T细胞的致敏CD 8缺陷小鼠在用变应原激发时增加支气管肺泡灌洗液中的AHR和嗜酸性粒细胞数量。相反，接受OT-1小鼠的CD 8（+）T细胞而不接受CD 4（+）T细胞的致敏CD 8缺陷小鼠在激发时出现AHR和支气管肺泡灌洗液中嗜酸性粒细胞数量减少。这些数据表明，CD 4（+）和CD 8（+）T细胞之间的相互作用，部分通过在致敏阶段的IL-4，是必不可少的CD 8（+）IL-13（+）T细胞依赖性AHR和气道过敏性炎症的发展。
CD4(+) T cells, particularly Th2 cells, play a pivotal role in allergic airway inflammation. However, the requirements for interactions between CD4+ and CD8(+) T cells in airway allergic inflammation have not been delineated. Sensitized and challenged OT-1 mice in which CD8(+) T cells expressing the transgene for the OVA(257-264) peptide (SIINFEKL) failed to develop airway hyperresponsiveness (AHR), airway eosinophilia, Th2 cytokine elevation, or goblet cell metaplasia. OT-1 mice that received naive CD4(+)IL-4(+) T cells but not CD4(+)IL-4(-) T cells before sensitization developed all of these responses to the same degree as wild-type mice. Moreover, recipients of CD4(+)IL-4(+) T cells developed significant increases in the number of CD8(+)IL-13(+) T cells in the lung, whereas sensitized OT-1 mice that received primed CD4(+) T cells just before challenge failed to develop these responses. Sensitized CD8-deficient mice that received CD8(+) T cells from OT-1 mice that received naive CD4(+) T cells before sensitization increased AHR and eosinophil numbers in bronchoalveolar lavage fluid when challenged with allergen. In contrast, sensitized CD8-deficient mice receiving CD8(+) T cells from OT-1 mice without CD4(+) T cells developed reduced AHR and eosinophil numbers in bronchoalveolar lavage fluid when challenged. These data suggest that interactions between CD4(+) and CD8(+) T cells, in part through IL-4 during the sensitization phase, are essential to the development of CD8(+)IL-13(+) T cell-dependent AHR and airway allergic inflammation.