Respiratory Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
J Intern Med. 2012 Jan;271(1):90-103. doi: 10.1111/j.1365-2796.2011.02414.x. Epub 2011 Jul 13.
Sarcoidosis is an inflammatory disorder in which elevated numbers of activated T cells are found in the lung. HLA-DRB1*0301(pos) (DR3(pos) ) patients are characterized by good prognosis and an accumulation of lung CD4(pos) T cells expressing the T-cell receptor (TCR) gene segment AV2S3. Our aim was to phenotype lung and blood T-cell subsets in distinct patient groups to better understand the function of these subsets.
Bronchoalveolar lavage (BAL) fluid and whole blood were obtained from a total of 22 patients with sarcoidosis, of whom 11 were DR3(pos) . Using eight-colour flow cytometry, phenotyping of T cells was performed with regard to CD3, CD4, CD8, CD25, CD27, CD45RO, CD57, CD69, CD103, FOXP3 and TCR AV2S3.
DR3(pos) patients had fewer FOXP3(pos) (regulatory) CD45RO(pos) (memory) BAL T cells than DR3(neg) patients. Fewer AV2S3(pos) T cells were FOXP3(pos) , compared with AV2S3(neg) cells, thus indicating an effector function and not a regulatory role for this subset. Fewer lung and blood AV2S3(pos) T cells were CD25(pos) CD27(pos) , and more were CD25(neg) CD27(neg) and CD69(pos) , compared with AV2S3(neg) T cells, indicating a higher degree of differentiation and activation in both compartments.
Our main findings were a lower proportion of regulatory T cells in DR3(pos) patients, together with the accumulation of AV2S3(pos) T cells with a highly activated effector phenotype in the lungs of these patients. This may provide for efficient elimination of a harmful antigen in DR3(pos) patients and could thus help to explain the spontaneous recovery typically seen in these patients.
结节病是一种炎症性疾病，其肺部存在大量活化的 T 细胞。HLA-DRB1*0301（pos）（DR3（pos））患者的预后良好，且肺部 CD4（pos）T 细胞积聚，表达 T 细胞受体（TCR）基因片段 AV2S3。我们的目的是对不同患者群体的肺部和血液 T 细胞亚群进行表型分析，以更好地了解这些亚群的功能。
共采集了 22 例结节病患者的支气管肺泡灌洗液（BAL）和全血，其中 11 例为 DR3（pos）。采用八色流式细胞术，对 CD3、CD4、CD8、CD25、CD27、CD45RO、CD57、CD69、CD103、FOXP3 和 TCR AV2S3 对 T 细胞进行表型分析。
DR3（pos）患者的 FOXP3（regulatory）CD45RO（memory）BAL T 细胞比 DR3（neg）患者少。与 AV2S3（neg）细胞相比，AV2S3（pos）T 细胞中 FOXP3（pos）的比例较少，这表明该亚群具有效应功能，而不是调节功能。与 AV2S3（neg）T 细胞相比，肺和血液中的 AV2S3（pos）T 细胞 CD25（pos）CD27（pos）较少，CD25（neg）CD27（neg）和 CD69（pos）较多，这表明两个部位的分化和激活程度更高。
我们的主要发现是 DR3（pos）患者的调节性 T 细胞比例较低，同时这些患者肺部积聚了具有高度活化效应表型的 AV2S3（pos）T 细胞。这可能有助于有效地消除 DR3（pos）患者体内的有害抗原，从而有助于解释这些患者通常自发恢复的现象。
