Miyahara Nobuaki, Takeda Katsuyuki, Kodama Taku, Joetham Anthony, Taube Christian, Park Jung-Won, Miyahara Satoko, Balhorn Annette, Dakhama Azzeddine, Gelfand Erwin W
Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
J Immunol. 2004 Feb 15;172(4):2549-58. doi: 10.4049/jimmunol.172.4.2549.
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 eosinophilia, 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.
分泌白细胞介素-4、白细胞介素-5和白细胞介素-13的辅助性T细胞2/CD4 T细胞在过敏性疾病中的作用已得到充分证实；然而，CD8(+) 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。本研究旨在确定经抗原致敏的CD8(+) T细胞在这些变应原诱导反应发展中的作用。通过腹腔注射使CD8缺陷（CD8(-/-)）小鼠和野生型小鼠对卵清蛋白（OVA）致敏，然后经气道用OVA攻击。与野生型小鼠相比，CD8(-/-)小鼠对吸入的乙酰甲胆碱的气道反应性显著降低，肺嗜酸性粒细胞增多减少，并且在体内支气管肺泡灌洗（BAL）液中以及体外经培养的支气管周围淋巴结（PBLN）细胞抗原刺激后，白细胞介素-13的产生均减少。用变应原致敏的CD8(+) T细胞重建致敏并攻击的CD8(-/-)小鼠，可完全恢复AHR、BAL嗜酸性粒细胞增多以及BAL和PBLN细胞培养上清液中白细胞介素-13水平的发展。相比之下，转移来自白细胞介素-13缺陷供体小鼠的未致敏CD8(+) T细胞或变应原致敏的CD8(+) T细胞则无法做到这一点。对肺以及PBLN T细胞进行细胞内细胞因子染色显示，CD8(+) T细胞是白细胞介素-13的来源。这些数据表明，经抗原致敏的CD8(+) T细胞是AHR和气道炎症充分发展所必需的，这似乎与这些致敏T细胞产生白细胞介素-13有关。
