TH1-mediated airway hyperresponsiveness independent of neutrophilic inflammation
TH1-mediated airway hyperresponsiveness independent of neutrophilic inflammation
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DOI：
10.1016/j.jaci.2004.10.046
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发表时间：
2005-02-01
影响因子：
14.2
通讯作者：
Marusic, S
中科院分区：
文献类型：
--
作者：
Cui, JQ;Pazdziorko, S;Marusic, S
背景：T（H）2介导的过敏性哮喘以嗜酸性粒细胞增多、粘液分泌过多和气道高反应性（AHR）为特征。虽然T（H）2细胞及其细胞因子在AHR中起着重要作用，但T（H）1细胞和中性粒细胞在AHR中的作用仍存在争议。目的：我们试图确定T（H）1细胞和中性粒细胞在AHR中的作用。从D011.10小鼠纯化卵清蛋白特异性CD 4（+）T细胞，分化成TO细胞，并注射到幼稚BALB/c，IL-4 RalphaKO，或IL-8 RKO小鼠。卵清蛋白抗原攻击后，肺样本中细胞因子mRNA水平，以及支气管肺泡灌洗液（BALF）中的炎性细胞类型和数量进行了测定。结果：T（H）1细胞诱导的AHR与T（H）2细胞一样强。它们还诱导以中性粒细胞为主的肺部炎症。当T（H）1细胞转移到IL-4 RalphaKO小鼠中时，AHR和炎症均未减少。当IL-8 RKO小鼠被用作T（H）1细胞的受体时，嗜中性粒细胞的数量大大减少，但AHR与野生型小鼠一样强。另一方面，地塞米松治疗对嗜中性粒细胞没有影响，但显著降低了AHR。结论：T（H）1细胞可诱导强AHR，且不依赖于IL-4和IL-13。AHR与BALF中淋巴细胞和巨噬细胞的存在有关，但与中性粒细胞无关。我们的研究结果指出了T（H）1细胞介导AHR的途径，而不依赖于嗜酸性炎症。
Background: T(H)2-mediated allergic asthma is characterized by eosinophilia, mucus overproduction, and airway hyperresponsiveness (AHR). Although it is clear that T(H)2 cells and their cytokines; play an important role in AHR, the roles of T(H)1 cells and neutrophils in AHR are controversial.Objective: We sought to determine the roles of T(H)1 cells and neutrophils in AHR.Methods: Ovalbumin-specific CD4(+) T cells were purified from DO11.10 mice, differentiated into TO cells, and injected into naive BALB/c, lL-4RalphaKO, or IL-8RKO mice. After ovalbumin antigen challenge, cytokine mRNA levels in lung samples, as well as inflammatory cell types and numbers in bronchoalveolar lavage fluid (BALF), were determined. AHR was assessed by measuring resistance in tracheostomized mice and enhanced pause in freely moving mice.Results: T(H)1 cells induced AHR as robust as T(H)2 cells. They also induced lung inflammation dominated by neutrophils. Neither AHR nor inflammation were reduced when T(H)1 cells were transferred into IL-4RalphaKO mice. When IL-8RKO mice were used as recipients of T(H)1 cells, neutrophilia was greatly reduced, but the AHR was as strong as that seen in wild-type mice. On the other hand, dexamethasone treatment had no effect on neutrophilia but has significantly reduced AHR. Reduction in AHR was accompanied by a reduction in the numbers of lymphocytes and macrophages in BALF.Conclusions: T(H)1 cells can induce strong AHR independent of IL-4 and IL-13. The AHR is associated with the presence of lymphocytes and macrophages, but not neutrophils, in BALF. Our results point to a pathway whereby T(H)1 cells mediate AHR independent of neutrophilic inflammation.