Hjelmström P, Giscombe R, Lefvert A K, Grünewald J, Pirskanen R, Sanjeevi C B
Department of Medicine and ,Department of Molecular Medicine, Karolinska Hospital, ,Microbiology and Tumour Biology Centre, and ,Department of Neurology, Söder Hospital, Karolinska Institute, Stockholm, Sweden.
Eur J Immunogenet. 1997 Jun;24(3):179-189. doi: 10.1111/j.1365-2370.1997.00254.x.
To characterize better the functional aspects of the HLA class II associations with myasthenia gravis (MG), T-cell receptor (TCR) V alpha/beta elements were studied in peripheral blood in 29 Swedish MG patients. HLA typing had previously been done using polymerase chain reaction with sequence-specific primers (PCR-SSP) or combined with sequence-specific oligonucleotide probes (PCR-SSO). The TCR V gene expression was determined by fluorescence-activated cell sorter (FACS) analysis using 12 monoclonal antibodies (mAb) that detected 30-40% of CD4+ and CD8+ T cells. No correlation between HLA-DQ genotype and TCR V elements could be found, nor was any restricted V gene usage seen. Fourteen (48%) of the patients had T cells showing signs of abnormal expansion in peripheral blood. There was an increased expression of TCR V gene elements in CD8+ T cells in patients (13/29) compared with CD4+ T cells in patients (5/29) (P < 0.05) and in unthymectomized patients compared with controls (14/56) (P < 0.005). TCR V gene expression was also increased in the CD8+ population in unthymectomized (7/8) compared with thymectomized patients (6/21) (P < 0.01). There was an increased expression in both CD4+ and CD8+ populations in unthymectomized patients (7/8, 88%), compared with thymectomized patients (7/21) (P < 0.05). We conclude that the abnormal T-cell expansion in peripheral blood could be a reflection of non-specific pathogenic processes in the muscle and thymus.
为了更好地描述人类白细胞抗原(HLA)Ⅱ类分子与重症肌无力(MG)相关的功能方面,对29例瑞典MG患者外周血中的T细胞受体(TCR)Vα/β元件进行了研究。此前已使用序列特异性引物聚合酶链反应(PCR-SSP)或结合序列特异性寡核苷酸探针(PCR-SSO)进行HLA分型。使用12种单克隆抗体(mAb)通过荧光激活细胞分选仪(FACS)分析来确定TCR V基因表达,这些单克隆抗体可检测30%-40%的CD4+和CD8+ T细胞。未发现HLA-DQ基因型与TCR V元件之间存在相关性,也未观察到V基因的限制性使用。14例(48%)患者的外周血T细胞显示出异常扩增的迹象。与患者的CD4+ T细胞(5/29)相比,患者的CD8+ T细胞(13/29)中TCR V基因元件的表达增加(P<0.05),与未行胸腺切除术的患者相比,对照组(14/56)中TCR V基因元件的表达也增加(P<0.005)。与行胸腺切除术的患者(6/21)相比,未行胸腺切除术的患者(7/8)的CD8+群体中TCR V基因表达也增加(P<0.01)。与行胸腺切除术的患者(7/21)相比,未行胸腺切除术的患者(7/8,88%)的CD4+和CD8+群体中的表达均增加(P<0.05)。我们得出结论,外周血中异常的T细胞扩增可能是肌肉和胸腺中非特异性致病过程的反映。