Mikhak Zamaneh, Fukui Mieko, Farsidjani Alireza, Medoff Benjamin D, Tager Andrew M, Luster Andrew D
Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
J Allergy Clin Immunol. 2009 Jan;123(1):67-73.e3. doi: 10.1016/j.jaci.2008.09.049. Epub 2008 Dec 4.
Recruitment of antigen-specific T(H)2 cells into the lung is critical for the development of allergic airway inflammation. Although CCR4 and CCR8 are preferentially expressed on T(H)2 cells and CCR4, CCR8, and CXCR3 ligands are increased in asthma, the specific relative contribution of these receptors to antigen-specific T(H)2 cell trafficking into the allergic lung is not known.
To determine the relative contribution of the chemokine receptors CCR4, CCR8, and CXCR3 to antigen-specific T(H)2 cell trafficking in a murine model of allergic pulmonary inflammation.
We used adoptive transfer experiments to compare the trafficking of wild-type antigen-specific T(H)2 cells with antigen-specific T(H)2 cells deficient in CCR4, CCR8, or CXCR3.
CCR4-deficient antigen-specific T(H)2 cells failed to traffic efficiently into the lung and the airways. In contrast, CCR8-deficient antigen-specific T(H)2 cells accumulated in these sites. Trafficking of CXCR3-deficient antigen-specific T(H)2 cells and CCR4-deficient and CCR8-deficient antigen-specific T(H)1 cells were comparable to their wild-type counterparts. Approximately 60% of IL-4-producing antigen-specific T cells expressed CCR4. Disruption of CCR4-mediated antigen-specific T(H)2 cell trafficking decreased the levels of T(H)2-type cytokines in the airways and reduced airway eosinophilia and mucus production.
Our study demonstrates that CCR4 is required for the efficient entry of antigen-specific T(H)2 cells into the lung and the airways in a murine model of allergic pulmonary inflammation.
抗原特异性辅助性T细胞2（T(H)2细胞）募集至肺脏对于过敏性气道炎症的发展至关重要。尽管CCR4和CCR8在T(H)2细胞上优先表达，且哮喘中CCR4、CCR8及CXCR3配体增加，但这些受体在抗原特异性T(H)2细胞向过敏性肺脏迁移中的具体相对作用尚不清楚。
确定趋化因子受体CCR4、CCR8和CXCR3在过敏性肺部炎症小鼠模型中抗原特异性T(H)2细胞迁移中的相对作用。
我们采用过继转移实验比较野生型抗原特异性T(H)2细胞与CCR4、CCR8或CXCR3缺陷的抗原特异性T(H)2细胞的迁移情况。
CCR4缺陷的抗原特异性T(H)2细胞无法有效迁移至肺脏和气道。相比之下，CCR8缺陷的抗原特异性T(H)2细胞在这些部位积聚。CXCR3缺陷的抗原特异性T(H)2细胞以及CCR4缺陷和CCR8缺陷的抗原特异性T(H)1细胞的迁移情况与其野生型对应细胞相当。约60%产生白细胞介素-4的抗原特异性T细胞表达CCR4。CCR4介导的抗原特异性T(H)2细胞迁移的破坏降低了气道中T(H)2型细胞因子的水平，并减少了气道嗜酸性粒细胞增多和黏液分泌。
我们的研究表明，在过敏性肺部炎症小鼠模型中，CCR4是抗原特异性T(H)2细胞有效进入肺脏和气道所必需的。
