Mizushima N, Kohsaka H, Nanki T, Ollier W E, Carson D A, Miyasaka N
First Department of Internal Medicine, School of Medicine, Tokyo Medical and Dental University, Japan.
Clin Exp Immunol. 1997 Dec;110(3):428-33. doi: 10.1046/j.1365-2249.1997.4331451.x.
Our previous studies have disclosed that the peripheral T cell receptor beta (TCRB) gene repertoires of RA monozygotic twins were similar. This suggested that the TCRBV repertoire is controlled primarily by genetic factors. Here, we examine how the combination of HLA and presence of RA influence the peripheral TCRB repertoire. Peripheral blood mononuclear cells from six pairs of healthy monozygotic twins, six pairs of monozygotic twins discordant for RA, and nine siblings of a large family, including three RA patients, were examined for their TCRB gene repertoires. Among healthy twins and siblings, the BV repertoires between HLA-identical pairs were significantly more similar than those of HLA-non-identical pairs. When RA-affected members were included, the repertoires of the HLA-identical pairs discordant for RA were dissimilar compared with those of healthy pairs. TCRBV-BJ combination repertoire analysis of CD4 and CD8 T cell subsets from the twins showed that the dissimilarity was primarily confined to CD8 T cells in the healthy identical twins, whereas it was seen in both CD4 and CD8 T cell subsets in the RA-discordant twins. These results suggest (i) the presence of RA modifies the genetically controlled TCR repertoire of peripheral T cells, and (ii) the RA-associated alterations appear to occur more frequently in CD4 T cells than in CD8 T cells.
我们之前的研究表明，类风湿关节炎（RA）单卵双胞胎的外周T细胞受体β（TCRB）基因库相似。这表明TCRBV基因库主要受遗传因素控制。在此，我们研究人类白细胞抗原（HLA）的组合及RA的存在如何影响外周TCRB基因库。检测了来自6对健康单卵双胞胎、6对患RA的不一致单卵双胞胎以及一个大家庭的9名兄弟姐妹（包括3名RA患者）的外周血单个核细胞的TCRB基因库。在健康双胞胎和兄弟姐妹中，HLA相同的双胞胎之间的BV基因库比HLA不同的双胞胎之间的BV基因库显著更相似。当纳入患RA的成员时，患RA的HLA相同的不一致双胞胎的基因库与健康双胞胎的基因库不同。对双胞胎的CD⁺和CD⁺T细胞亚群进行TCRBV - BJ组合基因库分析表明，健康同卵双胞胎中的差异主要局限于CD⁺T细胞，而在患RA的不一致双胞胎的CD⁺和CD⁺T细胞亚群中均可见差异。这些结果表明：（i）RA的存在改变了外周T细胞受遗传控制的TCR基因库；（ii）与RA相关的改变似乎在CD⁺T细胞中比在CD⁺T细胞中更频繁地发生。
