CD8+ T lymphocytes in lung tissue from patients with idiopathic pulmonary fibrosis -: art. no. 81
CD8+ T lymphocytes in lung tissue from patients with idiopathic pulmonary fibrosis -: art. no. 81
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DOI：
10.1186/1465-9921-6-81
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发表时间：
2005-07-24
影响因子：
5.8
通讯作者：
Papiris, SA
中科院分区：
文献类型：
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作者：
Daniil, Z;Kitsanta, P;Papiris, SA
背景：多项研究表明炎症在特发性肺纤维化（IPF）肺损伤的发病机制中发挥作用。实质性肺损伤导致力学和气体交换缺陷，临床表现为劳力性呼吸困难。对IPF炎症细胞的研究表明，嗜酸性粒细胞、中性粒细胞和CD 8 + TL可能与预后较差相关。我们希望通过定量免疫组织化学研究浸润的巨噬细胞，中性粒细胞和T淋巴细胞（TLs）亚群IPF患者肺组织中CD 3+、CD 4+和CD 8+的表达及其与肺功能指标和呼吸困难程度的相关性。12例IPF患者的手术活检用小鼠单克隆抗体进行免疫化学染色（抗-CD 68用于巨噬细胞，抗-弹性蛋白酶用于中性粒细胞，抗-CD 3、抗-CD 4、抗-CD 8分别用于CD 3 + TL、CD 4 + TL和CD 8 + TL）。通过观察者交互式计算机图像分析（桑巴舞显微图像处理器）确定阳性染色细胞的数量。细胞数量表示为免疫阳性核表面相对于组织内浸润细胞的总核表面的百分比（标记指数）。将细胞数量与生理指标[FEV 1、FVC、TLC、DLCO、PaO 2、PaCO 2和P（A-a）O-2]以及医学研究理事会（MRC）量表评估的呼吸困难评分进行相关性分析。弹性蛋白酶阳性细胞占总细胞的7.04% ± 1.1%，CD 68+细胞占16.6% ± 2%，CD 3 + TL占28.8% ± 7%，14.5 +/-4的CD 4 + TL和13.8 +/-4的CD 8 + TL。CD 8 + TL与FVC %预测值（r（s）=-0.67，p = 0.01）、TLC %预测值（r（s）=-0.68，p = 0.01）、DLCO %预测值（r（s）=-0.61，p = 0.04）和PaO 2（r（s）=-0.60，p = 0.04）呈负相关。CD 8 + T淋巴细胞与P（A-a）O-2（r（s）= 0.65，p = 0.02）、CD 8 + T淋巴细胞与MRC评分（r（s）= 0.63，p = 0.02）呈正相关。此外，CD 68+细胞与FVC %预测值（r（s）=-0.80，p = 0.002）和FEV1%预测值（r（s）=-0.68，p = 0.01）呈负相关。在UIP/IPF组织中浸润单核细胞，尤其是CD 8 + TL与呼吸困难的分级和疾病严重程度的功能参数相关，暗示它们可能在其发病机制中发挥作用。
Background: Several studies have implicated a role of inflammation in the pathogenesis of lung damage in idiopathic pulmonary fibrosis (IPF). Parenchymal lung damage leads to defects in mechanics and gas exchange and clinically manifests with exertional dyspnea. Investigations of inflammatory cells in IPF have shown that eosinophils, neutrophils and CD8+ TLs may be associated with worse prognosis. We wished to investigate by quantitative immunohistochemistry infiltrating macrophages, neutrophils and T lymphocytes (TLs) subpopulations (CD3+, CD4+ and CD8+) in lung tissue of patients with IPF and their correlation with lung function indices and grade of dyspnoea.Methods: Surgical biopsies of 12 patients with IPF were immunohistochemically stained with mouse monoclonal antibodies (anti-CD68 for macrophages, anti-elastase for neutrophils, and anti-CD3, anti-CD4, anti-CD8 for CD3+ TLs, CD4+ TLs, and CD8+ TLs respectively). The number of positively stained cells was determined by observer-interactive computerized image analysis (SAMBA microscopic image processor). Cell numbers were expressed in percentage of immunopositive nuclear surface in relation to the total nuclear surface of infiltrative cells within the tissue (labeling Index). Correlations were performed between cell numbers and physiological indices [FEV1, FVC, TLC, DLCO, PaO2, PaCO2 and P(A-a)O-2)] as well as dyspnoea scores assessed by the Medical Research Council (MRC) scale.Results: Elastase positive cells accounted for the 7.04% +/- 1.1 of total cells, CD68+ cells for the 16.6% +/- 2, CD3+ TLs for the 28.8% +/- 7, CD4+ TLs for the 14.5 +/- 4 and CD8+ TLs for the 13.8 +/- 4. CD8+ TLs correlated inversely with FVC % predicted (r(s) = -0.67, p = 0.01), TLC % predicted (r(s) = -0.68, p = 0.01), DLCO % predicted (r(s) = -0.61, p = 0.04), and PaO2 (r(s) = -0.60, p = 0.04). Positive correlations were found between CD8+ TLs and P(A-a)O-2 (r(s) = 0.65, p = 0.02) and CD8+ TLs and MRC score (r(s) = 0.63, p = 0.02). Additionally, CD68+ cells presented negative correlations with both FVC % predicted (r(s) = -0.80, p = 0.002) and FEV1 % predicted (r(s) = -0.68, p = 0.01).Conclusion: In UIP/IPF tissue infiltrating mononuclear cells and especially CD8+ TLs are associated with the grade of dyspnoea and functional parameters of disease severity implicating that they might play a role in its pathogenesis.