Kim G, Kohyama K, Tanuma N, Matsumoto Y
Department of Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Fuchu City, Japan.
Eur J Immunol. 1998 Sep;28(9):2751-9. doi: 10.1002/(SICI)1521-4141(199809)28:09<2751::AID-IMMU2751>3.0.CO;2-J.
In organ-specific autoimmune diseases, T cells involved in the disease development bear a particular type of TCR and infiltrate the target organ predominantly. However, it is difficult to identify disease-inducing T cells in peripheral blood lymphocytes (PBL) because such T cells are very few in number in a large pool of unrelated T cells. In the present study, we demonstrate that CDR3 spectratyping can identify experimental autoimmune encephalomyelitis (EAE)-specific patterns (oligoclonal expansion of Vbeta8.2 with the shortest CDR3) in PBL at the preclinical and clinical stages of acute EAE. Analysis of nucleotide and predicted amino acid sequences of Vbeta8.2 CDR3 of spectratype-derived clones revealed that CASSDSSYEQYFGPG, which is one of the representative sequences of encephalitogenic T cell clones, constituted the predominant population in both PBL and spinal cord T cells. In chronic relapsing EAE, the EAE-specific spectratype pattern in PBL was observed during the 1 st and 2nd attacks, but not at the remission and full recovery stage. These findings indicate that the spectratyping pattern in PBL reflects the disease activity of acute and chronic relapsing EAE. Thus, CDR3 spectratyping using PBL can be used for diagnosis and assessment of T cell-mediated autoimmune diseases and is applicable to human autoimmune diseases.
在器官特异性自身免疫性疾病中，参与疾病发展的T细胞具有特定类型的TCR，并主要浸润靶器官。然而，在外周血淋巴细胞（PBL）中很难鉴定出致病T细胞，因为在大量无关T细胞中，这类T细胞数量极少。在本研究中，我们证明CDR3谱型分析能够在急性实验性自身免疫性脑脊髓炎（EAE）的临床前期和临床阶段，鉴定出PBL中EAE特异性模式（Vbeta8.2的寡克隆扩增，其CDR3最短）。对谱型衍生克隆的Vbeta8.2 CDR3的核苷酸和预测氨基酸序列分析显示，致脑炎性T细胞克隆的代表性序列之一CASSDSSYEQYFGPG在PBL和脊髓T细胞中均占主要群体。在慢性复发性EAE中，PBL中的EAE特异性谱型模式在第1次和第2次发作期间被观察到，但在缓解期和完全恢复期未观察到。这些发现表明，PBL中的谱型模式反映了急性和慢性复发性EAE的疾病活动。因此，使用PBL进行CDR3谱型分析可用于诊断和评估T细胞介导的自身免疫性疾病，并适用于人类自身免疫性疾病。
