Garlepp M J, Rose A H, Dench J E, Robinson B W
Department of Medicine, University of Western Australia, Queen Elizabeth II Medical Centre, Nedlands.
Thorax. 1994 Jun;49(6):577-85. doi: 10.1136/thx.49.6.577.
Sarcoidosis is a disease characterised by clinical "anergy" to delayed type hypersensitivity antigens and the formation of non-caseating granulomas, which frequently manifests in the lungs as a T lymphocyte/mononuclear cell alveolitis. Although there is an increased proportion of T cells in bronchoalveolar lavage (BAL) samples from these patients, and these T cells often show evidence of activation and spontaneous secretion of cytokines such as interleukin 2 (IL-2) and interferon gamma (IFN gamma)--a pattern similar to delayed type hypersensitivity reactions--it is unclear whether both cytokines are produced by the majority of T cells derived from the lungs of patients with sarcoidosis or whether unique subpopulations of T cells produce each cytokine. In this study the properties of T cells cloned from BAL fluid samples of patients with sarcoidosis have been analysed.
T cells were cloned by limiting dilution using IL-2, phytohaemagglutinin, and irradiated feeder cells. Cloning efficiencies were compared and phytohaemagglutinin induced clonal production of IL-2, IFN gamma, and IL-4 was determined by bioassay (IL-2 and IFN gamma) or ELISA (IL-4).
T cells derived from the BAL fluid of patients with sarcoidosis cloned less efficiently than those from blood of the same individuals. Lung derived clones (CD4+ or CD8+) produced IFN gamma more frequently and to a higher titre than blood derived clones, whereas IL-2 production by CD4+ clones derived from BAL fluid was less than that from blood derived clones. Interestingly, IL-4 production by clones from both sites was similar. Analysis of the co-production of IL-2, IFN gamma, and IL-4 by these BAL fluid clones did not demonstrate a predominant "Th1"-like population which has been suggested to underlie delayed type hypersensitivity reactions.
The reduced cloning efficiency of T cells from the lung compared with the blood in sarcoidosis is consistent with, although probably more pronounced than, previous observations in normal lungs and shows that T cell hyporesponsiveness is not overcome in the lungs of patients with sarcoidosis. Furthermore, major differences exist between the cytokine producing potential of T cells derived from the lung and the blood in sarcoidosis, and these parallel the differences in the properties of blood and lung T cells seen in healthy individuals.
结节病是一种以对迟发型超敏反应抗原出现临床“无反应性”以及形成非干酪样肉芽肿为特征的疾病，常表现为肺部的T淋巴细胞/单核细胞肺泡炎。尽管这些患者支气管肺泡灌洗（BAL）样本中的T细胞比例增加，且这些T细胞常显示出活化迹象以及自发分泌白细胞介素2（IL - 2）和干扰素γ（IFNγ）等细胞因子——这一模式类似于迟发型超敏反应——但尚不清楚这两种细胞因子是否由大多数源自结节病患者肺部的T细胞产生，或者是否有独特的T细胞亚群分别产生每种细胞因子。在本研究中，对从结节病患者BAL液样本中克隆的T细胞特性进行了分析。
使用IL - 2、植物血凝素和经照射的饲养细胞通过有限稀释法克隆T细胞。比较克隆效率，并通过生物测定法（IL - 2和IFNγ）或酶联免疫吸附测定法（ELISA）（IL - 4）测定植物血凝素诱导的IL - 2、IFNγ和IL - 4的克隆产生情况。
源自结节病患者BAL液的T细胞克隆效率低于源自同一患者血液的T细胞。源自肺部的克隆（CD4 +或CD8 +）比源自血液的克隆更频繁且以更高滴度产生IFNγ，而源自BAL液的CD4 +克隆产生IL - 2的量少于源自血液的克隆。有趣的是，来自两个部位的克隆产生IL - 4的情况相似。对这些BAL液克隆中IL - 2、IFNγ和IL - 4的共同产生情况分析未显示出占主导的“Th1”样群体，而有人认为该群体是迟发型超敏反应的基础。
结节病患者肺部T细胞与血液中的T细胞相比克隆效率降低，这与先前在正常肺部的观察结果一致，尽管可能更明显，表明结节病患者肺部的T细胞低反应性未得到克服。此外，结节病中源自肺部和血液的T细胞产生细胞因子的潜力存在重大差异，且这些差异与健康个体中血液和肺部T细胞特性的差异相似。
