Leukotriene B4 receptor-1 is essential for allergen-mediated recruitment of CD8+ T cells and airway hyperresponsiveness
Leukotriene B4 receptor-1 is essential for allergen-mediated recruitment of CD8+ T cells and airway hyperresponsiveness
复制标题
DOI：
10.4049/jimmunol.174.8.4979
复制
发表时间：
2005-04-15
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
最近对人类和啮齿动物的研究表明，除了CD4(+) T细胞外，CD8(+) T细胞在过敏性炎症中起重要作用。我们之前证明，与野生型小鼠相比，过敏原致敏和CD8（-/-）挑战小鼠的气道高反应性（AHR）、嗜酸性炎症和支气管肺泡灌洗液中IL-13水平显著降低，并且所有这些反应都可以通过过继转移体内启动的CD8(+) T细胞或体外产生的效应CD8(+) T细胞（T- eff）来恢复。最近，白三烯B4及其高亲和受体BLT1已被证明可以介导体外生成的T-EEF向炎症组织的募集。在这项研究中，我们研究了BLT1是否对CD8(+) T细胞介导的过敏性AHR和炎症的发展至关重要。将体内启动的BLT1(+/+)，而不是BLTI-/-， CD8(+) T细胞过继转移到致敏和挑战的CD8（-/-）小鼠中，可恢复AHR，嗜酸性炎症和IL-13水平。此外，当将T-EFF过继转移到致敏的CD8（-/-）小鼠体内时，在体外产生BLTI+/+，而不是BLT1(-/-)， T-EFF在肺中积累，并介导这些对过敏原挑战的气道反应改变。这些数据首次显示了BLT1在过敏原介导的CD8(+) T-EFF向肺募集以及AHR和气道炎症的发展中具有功能性和必要的作用。
Recent studies in both human and rodents have indicated that in addition to CD4(+) T cells, CD8(+) T cells play an important role in allergic inflammation. We previously demonstrated that allergen-sensitized and -challenged CD8-deficient (CD8(-/-)) mice develop significantly lower airway hyperresponsiveness (AHR), eosinophilic inflammation, and IL-13 levels in bronchoalveolar lavage fluid compared with wild-type mice, and that all these responses were restored by adoptive transfer of in vivo-primed CD8(+) T cells or in vitro-generated effector CD8(+) T cells (T-EFF). Recently, leukotriene B4 and its high affinity receptor, BLT1, have been shown to mediate in vitro-generated T-EEF recruitment into inflamed tissues. In this study we investigated whether BLT1 is essential for the development of CD8(+) T cell-mediated allergic AHR and inflammation. Adoptive trans fer of in vivo-primed BLT1(+/+), but not BLTI-/-, CD8(+) T cells into sensitized and challenged CD8(-/-) mice restored AHR, eosinophilic inflammation, and IL-13 levels. Moreover, when adoptively transferred into sensitized CD8(-/-) mice, in vitro-generated BLTI+/+, but not BLT1(-/-), T-EFF accumulated in the lung and mediated these altered airway responses to allergen challenge. These data are the first to show both a functional and an essential role for BLT1 in allergen-mediated CD8(+) T-EFF recruitment into the lung and development of AHR and airway inflammation.