Contribution of antigen-primed CD8+ T cells to the development of airway hyperresponsiveness and inflammation is associated with IL-13
Contribution of antigen-primed CD8+ T cells to the development of airway hyperresponsiveness and inflammation is associated with IL-13
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DOI：
10.4049/jimmunol.172.4.2549
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发表时间：
2004-02-15
影响因子：
4.4
通讯作者：
Gelfand, EW
中科院分区：
文献类型：
--
作者：
Miyahara, N;Takeda, K;Gelfand, EW
分泌IL-4、IL-5和IL-13的Th 2/CD 4 T细胞在变应性疾病中的作用已得到充分证实;然而，CD 8（+）T细胞（变应原诱导的气道高反应性（AHR）和炎症）的作用尚不清楚。本研究旨在确定Ag致敏的CD 8（+）T细胞在这些变应原诱导的反应中的作用。通过腹膜内注射使CD 8缺陷型（CD 8（-/-））小鼠和野生型小鼠对OVA致敏，然后通过气道用OVA激发。与野生型相比。CD 8（-/-）小鼠对吸入乙酰甲胆碱和肺嗜酸性粒细胞增多症的气道反应性显著降低，并且在体内、支气管肺泡灌洗液（BAL）中和体外培养的支气管周围淋巴结（PBLN）细胞的Ag刺激后，表现出IL-13产生减少。用过敏原致敏的CD 8（+）T细胞重建致敏和激发的CD 8（-/-）小鼠，完全恢复了AHR、BAL嗜嗜糖蛋白和BAL中以及PBLN细胞培养上清液中IL-13水平的发展。相比之下，从IL-13缺陷的供体小鼠转移初始CD 8（+）T细胞或变应原致敏的CD 8（+）T细胞则不能做到这一点。肺以及PBLN T细胞的细胞内细胞因子染色揭示了CD 8（+）T细胞是IL-13的来源。这些数据表明，Ag致敏的CD 8（+）T细胞是AHR和气道炎症完全发展所必需的，这似乎与这些致敏的T细胞产生IL-13有关。免疫学杂志，2004，172：2549-2558.
The role of Th2/CD4 T cells, which secrete IL-4, IL-5, and IL-13, in allergic disease is well established; however, the role of CD8(+) T cells (allergen-induced airway hyperresponsiveness (AHR) and inflammation) is less clear. This study was conducted to define the role of Ag-primed CD8(+) T cells in the development of these allergen-induced responses. CD8-deficient (CD8(-/-)) mice and wild-type mice were sensitized to OVA by i.p. injection and then challenged with OVA via the airways. Compared with wild-type. mice, CD8(-/-) mice developed significantly lower airway responsiveness to inhaled methacholine and lung eosinophilia, and exhibited decreased IL-13 production both in vivo, in the bronchoalveolar lavage (BAL) fluid, and in vitro, following Ag stimulation of peribronchial lymph node (PBLN) cells in culture. Reconstitution of sensitized and challenged CD8(-/-) mice with allergen-sensitized CD8(+) T cells fully restored the development of AHR, BAL cosinophilia, and IL-13 levels in BAL and in culture supernatants from PBLN cells. In contrast, transfer of naive CD8(+) T cells or allergen-sensitized CD8(+) T cells from IL-13-deficient donor mice failed to do so. Intracellular cytokine staining of lung as well as PBLN T cells revealed that CD8(+) T cells were a source of IL-13. These data suggest that Ag-primed CD8(+) T cells are required for the full development of AHR and airway inflammation, which appears to be associated with IL-13 production from these primed T cells. The Journal of Immunology, 2004, 172: 2549-2558.