Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Smith Research Building, Room 616, One Jimmy Fund Way, Boston, MA 02115, USA.
J Immunol. 2010 Aug 1;185(3):1804-11. doi: 10.4049/jimmunol.1001146. Epub 2010 Jul 2.
In C57BL/6 mice, the recruitment of mast cell progenitors (MCps) to the lung is a feature of Ag-induced pulmonary inflammation that requires sensitization and challenge and is totally inhibited by the administration of anti-CD4 at the time of challenge. When mAb to TGFbeta1 or to IL-10R was administered at the time of challenge, the recruitment of MCp/10(6) mononuclear cells (MNCs) to the lung was inhibited by 56.3 and 69.6%, respectively, whereas mAb to IL-4, IFN-gamma, IL-6, IL-17A, and IL-17F had no effect. In sensitized and challenged C57BL/6 mice lacking TGFbetaRII on CD4(+) cells, the recruitment of MCp/10(6) MNCs was reduced by 67.8%. The requirement for TGFbeta1 and IL-10 suggested a role for CD4(+)CD25(+) T regulatory cells. Mice treated with anti-CD25 at the time of Ag-challenge showed a reduction in the recruitment of MCp/10(6) MNCs by 77.2% without any reduction in MNC influx. These results reveal an unexpected role for T regulatory cells in promoting the recruitment of MCps to the lungs of C57BL/6 mice with Ag-induced pulmonary inflammation.
在 C57BL/6 小鼠中，肥大细胞祖细胞（MCps）向肺部的募集是 Ag 诱导的肺部炎症的一个特征，需要致敏和挑战，并且在挑战时给予抗 CD4 完全抑制。当在挑战时给予 TGFbeta1 或 IL-10R 的 mAb 时，MCp/10(6)单核细胞（MNC）向肺部的募集分别被抑制 56.3%和 69.6%，而抗 IL-4、IFN-gamma、IL-6、IL-17A 和 IL-17F 没有效果。在致敏和挑战的 C57BL/6 小鼠中，CD4(+)细胞上缺乏 TGFbetaRII 时，MCp/10(6)MNC 的募集减少了 67.8%。对 TGFbeta1 和 IL-10 的需求表明 CD4(+)CD25(+)T 调节细胞发挥了作用。在 Ag 挑战时用抗 CD25 治疗的小鼠显示 MCp/10(6)MNC 的募集减少了 77.2%，而 MNC 流入没有减少。这些结果揭示了 T 调节细胞在促进 Ag 诱导的肺部炎症的 C57BL/6 小鼠中 MCps 向肺部募集中的意外作用。
