Essential Contribution of CD4+ T Cells to Antigen-Induced Nasal Hyperresponsiveness in Experimental Allergic Rhinitis.
Essential Contribution of CD4+ T Cells to Antigen-Induced Nasal Hyperresponsiveness in Experimental Allergic Rhinitis.
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DOI：
10.1371/journal.pone.0146686
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Hiroi T
中科院分区：
文献类型：
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作者：
Nishimura T;Kaminuma O;Saeki M;Kitamura N;Matsuoka K;Yonekawa H;Mori A;Hiroi T
鼻高反应性（NHR）是变应性鼻炎（AR）的特征性表现；然而，NHR的发病机制尚不完全清楚。在本研究中，在使用卵清蛋白免疫和激振小鼠建立实验性AR模型时，检测到非特异性蛋白质和化学刺激物对打喷嚏反应的增强。通过使用肥大细胞和嗜酸性粒细胞缺陷小鼠来确定NHR是否独立于肥大细胞和嗜酸性粒细胞。抗CD4抗体抑制NHR，提示CD4+ T细胞的关键作用。此外，对体外分化的Th1、Th2和Th17细胞而不是naïve CD4+ T细胞过继转移的小鼠进行抗原刺激可导致等效NHR的发展。由于在这些小鼠中没有产生抗原特异性IgE和IgG，并且抗原特异性IgE转基因小鼠即使在抗原攻击下也不会发生NHR，因此对于NHR来说，体液免疫是必不可少的。CD4+ T细胞通过诱导NHR在AR的发病机制中发挥关键作用，独立于IgE、肥大细胞和嗜酸性粒细胞介导的反应。
Nasal hyperresponsiveness (NHR) is a characteristic feature of allergic rhinitis (AR); however, the pathogenesis of NHR is not fully understood. In this study, during the establishment of an experimental AR model using ovalbumin-immunized and -challenged mice, augmentation of the sneezing reaction in response to nonspecific proteins as well as a chemical stimulant was detected. Whether NHR is independent of mast cells and eosinophils was determined by using mast cell- and eosinophil-deficient mice. NHR was suppressed by treatment with anti-CD4 antibody, suggesting the pivotal contribution of CD4+ T cells. Furthermore, antigen challenge to mice to which in vitro-differentiated Th1, Th2, and Th17 cells but not naïve CD4+ T cells had been adoptively transferred led to the development of equivalent NHR. Since antigen-specific IgE and IgG were not produced in these mice and since antigen-specific IgE-transgenic mice did not develop NHR even upon antigen challenge, humoral immunity would be dispensable for NHR. CD4+ T cells play a crucial role in the pathogenesis of AR via induction of NHR, independent of IgE-, mast cell-, and eosinophil-mediated responses.