Facco Monica, Trentin Livio, Nicolardi Linda, Miorin Marta, Scquizzato Elisa, Carollo Davide, Baesso Ilenia, Bortoli Michela, Zambello Renato, Marcer Guido, Agostini Carlo, Semenzato Gianpietro
Department of Clinical and Experimental Medicine, Clinical Immunology Branch, Padova, Italy.
J Leukoc Biol. 2004 May;75(5):798-804. doi: 10.1189/jlb.0503218. Epub 2004 Feb 13.
Hypersensitivity pneumonitis (HP) is characterized by an alveolitis sustained by CD8(+) T lymphocytes showing a limited expression of the T cell receptor (TCR). We previously demonstrated that a bias in T cell selection occurs in the lower respiratory tract of patients with HP, with a compartmentalization in the lung of CD8(+) T cells bearing (TCR)-beta variable (TCRBV) #2, 3, 5, 6, 8, and 13 gene segments. We herein characterized the clonal T cell populations present in the lung and in the blood of patients with HP. Heteroduplex analyses, cloning, and sequencing T cells bearing TCR indicate oligoclonal expansions of T cells expressing homologous or identical complementary-determining region 3. Furthermore, T cell clones isolated from the two compartments expressed similar, sometimes identical, junctional regions. Removal from antigenic exposure led to the disappearance of T cell clones. Our findings indicate that expansions of T lymphocytes bearing clonal TCRBV region gene segments take place in the lung of patients with HP during exposure. The evidence that identical T cell clones are present in the lung and the blood of the same patient suggests that the immune reaction occurring at lung level gives rise to a systemic reaction.
过敏性肺炎(HP)的特征是由CD8(+) T淋巴细胞维持的肺泡炎,这些T淋巴细胞显示出有限的T细胞受体(TCR)表达。我们之前证明,HP患者的下呼吸道会发生T细胞选择偏向,肺部存在携带TCR-β可变区(TCRBV)#2、3、5、6、8和13基因片段的CD8(+) T细胞分区。我们在此对HP患者肺部和血液中的克隆性T细胞群体进行了表征。对携带TCR的T细胞进行异源双链分析、克隆和测序表明,表达同源或相同互补决定区3的T细胞出现寡克隆扩增。此外,从两个分区分离出的T细胞克隆表达相似、有时相同的连接区。去除抗原暴露会导致T细胞克隆消失。我们的研究结果表明,在暴露期间,HP患者肺部会出现携带克隆性TCRBV区域基因片段的T淋巴细胞扩增。同一患者的肺部和血液中存在相同T细胞克隆的证据表明,肺部发生的免疫反应会引发全身反应。