Sieling P A, Sakimura L, Uyemura K, Yamamura M, Oliveros J, Nickoloff B J, Rea T H, Modlin R L
Division of Dermatology, University of California, Los Angeles, School of Medicine, CA 90095.
J Immunol. 1995 Mar 15;154(6):2775-83.
The goal of the present study was to investigate the role of IL-7 in regulating immune responses to infection. Leprosy provides a model for understanding human immune responses to infection; the disease presents as a spectrum in which the clinical manifestations correlate with the levels of cell-mediated immunity to the pathogen, Mycobacterium leprae. To determine whether IL-7 is produced at the site of infection in leprosy, we used the PCR to measure IL-7 and IL-7R mRNA in skin lesions. IL-7 mRNA was more strongly expressed in the tuberculoid form of the disease, in which the infection is limited (mean cpm = 48 +/- 8; n = 11), as compared with the progressive lepromatous form (17 +/- 2; n = 11). IL-7R mRNA, both membrane-bound and soluble forms, were also more strongly expressed in tuberculoid lesions, although these differences were not as striking as those for IL-7. The cellular source of IL-7 included Ag-stimulated monocytes and IFN-gamma-induced keratinocytes. M. leprae-induced PBMC responses in tuberculoid patients involved up-regulation of IL-7 and IL-7R mRNA and was IL-7 dependent. In contrast, M. leprae did not induce IL-7 mRNA in lepromatous patients, and their T cell responses were weakly augmented by rIL-7. These data suggest that IL-7, produced at the site of disease, contributes to the cell-mediated immune response to human pathogens.
本研究的目的是调查白细胞介素-7（IL-7）在调节感染免疫反应中的作用。麻风病为理解人类对感染的免疫反应提供了一个模型；该疾病呈现为一种谱系，其中临床表现与对病原体麻风分枝杆菌的细胞介导免疫水平相关。为了确定麻风病感染部位是否产生IL-7，我们使用聚合酶链反应（PCR）来测量皮肤病变中IL-7和IL-7受体（IL-7R）的信使核糖核酸（mRNA）。与进行性瘤型麻风（平均每分钟脉冲数 = 17 ± 2；n = 11）相比，在感染受限的结核样型麻风病中，IL-7 mRNA表达更强（平均每分钟脉冲数 = 48 ± 8；n = 11）。膜结合型和可溶性形式的IL-7R mRNA在结核样病变中也表达更强，尽管这些差异不如IL-7明显。IL-7的细胞来源包括抗原刺激的单核细胞和干扰素-γ诱导的角质形成细胞。结核样型患者中麻风分枝杆菌诱导的外周血单核细胞（PBMC）反应涉及IL-7和IL-7R mRNA的上调，并且依赖于IL-7。相比之下，瘤型麻风患者中麻风分枝杆菌不诱导IL-7 mRNA，并且其T细胞反应仅被重组IL-7轻微增强。这些数据表明，在疾病部位产生的IL-7有助于对人类病原体的细胞介导免疫反应。
