TCR expression of activated T cell clones in the lungs of patients with pulmonary sarcoidosis.
TCR expression of activated T cell clones in the lungs of patients with pulmonary sarcoidosis.
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DOI：
10.4049/jimmunol.153.9.4291
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发表时间：
1994-11
影响因子：
4.4
通讯作者：
J. M. Forrester;J. M. Forrester;Yi Wang;N. Ricalton;J. Fitzgerald;J. Loveless;J. Loveless;L. Newman;L. Newman;T. King;T. King;B. Kotzin;B. Kotzin
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文献类型：
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作者：
J. M. Forrester;J. M. Forrester;Yi Wang;N. Ricalton;J. Fitzgerald;J. Loveless;J. Loveless;L. Newman;L. Newman;T. King;T. King;B. Kotzin;B. Kotzin
结节病是一种病因不明的系统性肉芽肿性疾病，其中CD4+ T细胞似乎至关重要。在肺部疾病患者的肺部，CD4+ T细胞大量积聚，其中一部分细胞被激活。通过定量PCR和抗v β单克隆抗体，我们分析了总T细胞和活化的支气管肺泡灌洗T细胞的TCR库，后者是通过在补充IL-2的短期培养中增殖的能力来定义的。总的来说，在个体患者中比较新鲜分离的肺细胞和外周血细胞的TCR V β表达时，差异不大。一些个体确实表现出少量V β表达亚群的适度增加。然而，在il -2补充培养基中体外生长1至2周后，大多数患者的支气管肺泡灌洗细胞（而不是来自任何健康个体）表现出特定V β表达亚群的选择性扩增。有趣的是，在不同的患者中，不同的携带V β的亚群扩展。连接区测序表明，培养中增殖的T细胞明显是寡克隆的，并且来源于已经在体内选择性扩增的T细胞克隆。这些结果为CD4+ T细胞的特定亚群对局部Ag的识别提供了疾病过程的证据。分析这些il -2扩增人群的Ag特异性可能有助于深入了解这种疾病的发病机制。
Sarcoidosis is a systemic granulomatous disease of unknown etiology in which CD4+ T cells seem to be critically involved. In the lungs of patients with pulmonary disease, CD4+ T cells accumulate in large numbers, and a subset of these cells is activated. By using both quantitative PCR and anti-V beta mAbs, we analyzed the TCR repertoire of total and activated bronchoalveolar lavage T cells, the latter subset being defined by the ability to proliferate in short-term culture supplemented with IL-2. Overall, there was little difference when TCR V beta expression of freshly isolated lung and peripheral blood cells was compared in individual patients. Some individuals did demonstrate a modest increase in a few V beta-expressing subsets. However, after 1 to 2 wk of in vitro growth in IL-2-supplemented media, bronchoalveolar lavage cells from most patients, but not from any healthy individuals, demonstrated a selective expansion of particular V beta-expressing subsets. Interestingly, different V beta-bearing subsets were expanded in different patients. Junctional region sequencing indicated that the proliferating T cells in culture were strikingly oligoclonal and were derived from T cell clones already selectively expanded in vivo. These results provide evidence for a disease process that involves recognition of local Ag(s) by specific subsets of CD4+ T cells. Analysis of the Ag specificity of these IL-2-expanded populations is likely to provide insight into the pathogenesis of this disease.