Vγ1＋γδ T淋巴细胞对气道变应性炎症和气道高反应性的调节

Regulation of allergic airway inflammation and hyperreactivity by Vγ1^+γδ T cells

目的:探讨消除Vγ1+γδT淋巴细胞的哮喘C57BL/6小鼠中观察气道高反应性和支气管灌洗液中细胞因子浓度变化、肺组织中CD4+CD25+T淋巴细胞变化。方法:T淋巴细胞消除是以OVA首次致敏和第二次致敏1周前注射anti-Vγ1mAbs、anti-Vγ4 mAbs、nonspecific hanmster IgG来完成。对C57BL/6小鼠测定气道高反应性后留取支气管灌洗液,分离肺组织。采用ELISA法测定支气管灌洗液中IL-10和TGF-β的浓度,利用FACS分析肺组织中提取的CD4+CD25+T淋巴细胞。结果:(1)诱导哮喘时消除Vγ1+γδT淋巴细胞的C57BL/6小鼠气道高反应性比注射hanmster IgG的对照组减弱。但是消除Vγ4+γδT淋巴细胞的C57BL/6小鼠气道高反应性与对照组相比无差别。(2)消除Vγ1+γδT淋巴细胞的C57BL/6小鼠支气管灌洗液中IL-10和TGF-β浓度比对照组增加。(3)消除Vγ1+γδT淋巴细胞的C57BL/6小鼠肺组织中CD4+CD25+T淋巴细胞比对照组明显增加。结论:消除Vγ1+γδT淋巴细胞的哮喘C57BL/6小鼠气道高反应性减弱与支气管灌洗液中细胞因子IL-10和TGF-β的增加有关,并且与肺组织中的调节T淋巴细胞CD4+CD25+T淋巴细胞增加有关。

Objective： To investigate the changes of airway hypersensitivity（AHR） and of CD4^＋ CD25^＋ regulatory T cells in the lung parenehymal tissue and another regulatory cytokine, TGF-β,in the airway in ovalbumin（OVA） sensitized and challenged C57BL/6 mice when initiated before i.p. sensitization by depletion of Vγ1＋γδ T cells. Methods： T cell depletion was achieved by injection of anti-Vγ1 mAbs, anti- Vγ4 mAbs, or nonspecitic hamster IgG at the 1 week before the first OVA sensitization, and 1 week before the second OVA sensitization. After determination of AHR, lungs were lavaged for differential counts and eytokine assay and digested for flow eytometrie analysis ofCD4^＋ CD25^＋ T cells. Results： Depletion of Vγ1＋γδ T cells resulted in decrease of AHR although depletion Vγ1＋γδ T cells did not induce any changes in AHR. Airway IL-10 and TGF-β levels were detected to be increased in mice depleted of Vγ1＋γδ T cells. OVA sensitized and challenged mice had significantly higher numbers ofhmg tissue CD4^＋ CD25^＋ T cells compared with those of naive or OVA non-sensitized and challenged mice. The increase of CD4^＋ CD25^＋ T cells was more remarkable in Vγ1＋γδ T cells-depleted mice than in sham-treated or Vγ1＋γδ T cells-depleted mice. Conclusioa：This study presents strong evidence that Vγ1＋γδ T cells are crucial in maintaining allergic response by regulation of CD4^＋ CD25^＋ T cell,IL-10 and TGF-β.