Grunewald J, Olerup O, Persson U, Ohrn M B, Wigzell H, Eklund A
Microbiology and Tumorbiology Center, Karolinska Institute, Stockholm, Sweden.
Proc Natl Acad Sci U S A. 1994 May 24;91(11):4965-9. doi: 10.1073/pnas.91.11.4965.
Sarcoidosis is a chronic noncaseating granulomatous disease of unknown etiology. An accumulation of CD4+ T cells in the alveolar space of the lungs is a characteristic feature of the disease. We have in this study analyzed T-cell receptor (TCR) variable region (V) gene usage by CD4+ and CD8+ lung and peripheral blood T cells of 29 sarcoidosis patients and 15 control subjects. In the patient group, we found a 100% positive correlation between TCR V alpha 2.3+ CD4+ lung T-cell expansions and the expression of the HLA-DR3(17),DQ2 haplotype. The remaining TCR V alpha/V beta gene products analyzed in this study--V alpha 12, V beta 2, V beta 3, V beta 5.1, V beta 5.2/5.3, V beta 5.3, V beta 6.7, V beta 8.1, and V beta 12--were in general normally expressed by CD4+ T cells, although some of them were used to a significantly higher or lower degree by lung T cells compared to peripheral blood T cells. We also performed repeated TCR V gene analyses on some HLA-DR3+ patients and found an association between the ratio bronchoalveolar lavage fluid/peripheral blood V alpha 2.3+ CD4+ T cells and clinical signs of disease activity. Finally, when analyzing TCR V gene usage by CD8+ bronchoalveolar lavage fluid and peripheral blood T cells, a normal V alpha 2.3 usage was found in all cases, but lung-restricted T-cell expansions using other TCR V gene segment products were identified.
结节病是一种病因不明的慢性非干酪样肉芽肿性疾病。肺肺泡腔内CD4+ T细胞的积聚是该疾病的一个特征性表现。在本研究中，我们分析了29例结节病患者和15名对照受试者的肺及外周血CD4+和CD8+ T细胞的T细胞受体（TCR）可变区（V）基因使用情况。在患者组中，我们发现TCR Vα2.3+ CD4+肺T细胞扩增与HLA-DR3(17)、DQ2单倍型的表达之间存在100%的正相关。本研究中分析的其余TCR Vα/Vβ基因产物——Vα12、Vβ2、Vβ3、Vβ5.1、Vβ5.2/5.3、Vβ5.3、Vβ6.7、Vβ8.1和Vβ12——通常由CD4+ T细胞正常表达，尽管与外周血T细胞相比，其中一些在肺T细胞中的使用程度明显更高或更低。我们还对一些HLA-DR3+患者进行了重复的TCR V基因分析，发现支气管肺泡灌洗液/外周血Vα2.3+ CD4+ T细胞的比例与疾病活动的临床体征之间存在关联。最后，在分析CD8+支气管肺泡灌洗液和外周血T细胞的TCR V基因使用情况时，所有病例中均发现Vα2.3的正常使用，但鉴定出了使用其他TCR V基因片段产物的肺限制性T细胞扩增。
