Regulatory role of B cells in a murine model of allergic airway disease
Regulatory role of B cells in a murine model of allergic airway disease
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DOI：
10.4049/jimmunol.180.11.7318
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发表时间：
2008-06-01
影响因子：
4.4
通讯作者：
Schramm, Craig M.
中科院分区：
文献类型：
--
作者：
Singh, Anurag;Carson, William F.;Schramm, Craig M.
对 OVA 敏感并遭受急性 OVA 气溶胶暴露的小鼠会出现过敏性气道疾病 (AAD)。然而，长期持续接触 Ag 会导致 AAD 消退和局部吸入耐受 (LIT) 的发展。因为我们之前在该模型的消退阶段观察到 B 细胞在支气管肺泡灌洗 (BAL) 和肺门淋巴结 (HLN) 中的持续存在，所以我们研究了 B 细胞在 AAD 调节中的作用。尽管 B 细胞缺陷小鼠发生了 LIT，但将 HLN B 细胞从 LIT 小鼠过继转移至 OVA 致敏受体后，在随后的 OVA 气溶胶暴露后，可导致 AAD 减弱，具体表现为 BAL 白细胞增多和嗜酸性粒细胞增多、组织炎症减少以及乙酰甲胆碱高反应性缺失。在类似的过继转移研究中，来自 AAD 小鼠的 HLN B 细胞没有效果。 LIT HLN B细胞传递的保护作用是Ag特异性的，并且与BAL和HLN中Foxp3(+) T调节细胞的局部积累相关，但与脾脏中的全身性积累无关。过继转移前 LIT HLN B 细胞的荧光标记表明这些细胞具有迁移至局部炎症部位的能力。体外评估表明，LIT HLN B 细胞通过 TGF-β 诱导 CD4(+)CD25(-) T 效应细胞转化为功能性抑制性 CD4(+)CD25(+)Foxp3(+) T 调节细胞来发挥这种调节作用。这些发现说明了 AAD 中区域 B 细胞的新调节作用，并表明 B 细胞以及其他细胞类型在 LIT 的建立中可能发挥重要作用。
Mice sensitized to OVA and subjected to acute OVA aerosol exposures develop allergic airway disease (AAD). However, chronic continuous Ag exposure results in resolution of AAD and the development of local inhalational tolerance (LIT). Because we have previously observed the persistence of B cells in the bronchoalveolar lavage (BAL) and hilar lymph nodes (HLN) at the resolution stage of this model, we investigated the role of B cells in the modulation of AAD. Although B cell-deficient mice developed LIT, adoptive transfer of HLN B cells from LIT mice to OVA-sensitized recipients resulted in attenuated AAD following subsequent OVA aerosol exposure, as determined by reduced BAL leukocytosis and eosinophilia, decreased tissue inflammation, and absent methacholine hyper-responsiveness. In similar adoptive transfer studies, HLN B cells from AAD mice were without effect. The protection transferred by LIT HLN B cells was Ag specific and was associated with accumulation of Foxp3(+) T regulatory cells regionally in BAL and HLN, but not systemically in the spleen. Fluorescent labeling of LIT HLN B cells before adoptive transfer demonstrated that these cells had the capacity to migrate to local inflammatory sites. In vitro assessment demonstrated that the LIT HLN B cells exerted this regulatory effect via TGF-beta induced conversion of CD4(+)CD25(-) T effector cells into functionally suppressive CD4(+)CD25(+)Foxp3(+) T regulatory cells. These findings illustrated a novel regulatory role for regional B cells in AAD and suggested a possible contributory role of B cells, along with other cell types, in the establishment of LIT.