Agostini C, Cassatella M, Zambello R, Trentin L, Gasperini S, Perin A, Piazza F, Siviero M, Facco M, Dziejman M, Chilosi M, Qin S, Luster A D, Semenzato G
Department of Clinical and Experimental Medicine, Padova University School of Medicine, Italy.
J Immunol. 1998 Dec 1;161(11):6413-20.
The accumulation of T cells and monocytes at sites of ongoing inflammation represents the earliest step in the series of events that lead to granuloma formation in sarcoidosis. In this study, we evaluated the pulmonary production of IFN-inducible protein 10 (IP-10), a CXC chemokine that stimulates the directional migration of activated T cells. Striking levels of IP-10 were demonstrated in the bronchoalveolar lavage (BAL) fluid of 24 patients with pulmonary sarcoidosis and lymphocytic alveolitis, as compared with patients with inactive disease or control subjects. A positive correlation was demonstrated between IP-10 levels and the number of sarcoid CD45R0+/CD4+ cells in the BAL. Immunochemistry, performed with an anti-human IP-10 polyclonal Ab in lymph nodes displaying prominent sarcoid granulomas, showed that cells bearing IP-10 were mainly epithelioid cells and CD68+ macrophages located inside granulomatous areas. Macrophages recovered from the BAL of sarcoid patients stained positive for IP-10 protein. Furthermore, alveolar macrophages isolated from sarcoid patients with T cell alveolitis and cultured for 24 h in presence of IFN-gamma secreted definite levels of IP-10 capable of inducing T cell chemiotaxis. Interestingly, alveolar lymphocytes recovered from patients with active sarcoidosis were CD4+ T cells expressing Th1 cytokines (IL-2 and IFN-gamma) and high levels of CXCR3. Taken together, these data suggest the potential role of IP-10 in regulating the migration and activation of T cells toward sites of sarcoid inflammatory process and the consequent granuloma formation.
T细胞和单核细胞在持续炎症部位的积聚是结节病中导致肉芽肿形成的一系列事件的最早步骤。在本研究中，我们评估了IFN诱导蛋白10（IP-10）的肺脏产生情况，IP-10是一种CXC趋化因子，可刺激活化T细胞的定向迁移。与非活动性疾病患者或对照受试者相比，24例肺结节病和淋巴细胞性肺泡炎患者的支气管肺泡灌洗（BAL）液中显示出显著水平的IP-10。BAL中IP-10水平与结节病CD45R0+/CD4+细胞数量之间呈正相关。在显示明显结节病肉芽肿的淋巴结中用抗人IP-10多克隆抗体进行免疫化学分析，结果显示携带IP-10的细胞主要是位于肉芽肿区域内的上皮样细胞和CD68+巨噬细胞。从结节病患者的BAL中回收的巨噬细胞对IP-10蛋白染色呈阳性。此外，从患有T细胞肺泡炎的结节病患者中分离出的肺泡巨噬细胞在存在IFN-γ的情况下培养24小时，分泌出一定水平的能够诱导T细胞趋化的IP-10。有趣的是，从活动性结节病患者中回收的肺泡淋巴细胞是表达Th1细胞因子（IL-2和IFN-γ）和高水平CXCR3的CD4+T细胞。综上所述，这些数据表明IP-10在调节T细胞向结节病炎症过程部位的迁移和活化以及随后的肉芽肿形成中具有潜在作用。
