Elovaara I, Utz U, Smith S, Jacobson S
Department of Neurology, Tampere University Hospital, Finland.
J Neuroimmunol. 1995 Dec;63(1):47-53. doi: 10.1016/0165-5728(95)00129-8.
T cell receptor (TCR) V alpha and V beta chain usage of HTLV-I tax-specific, HLA class I restricted CD8+ cytotoxic T cells (CTL) was determined from lymphocytes obtained from peripheral blood of patients with HTLV-I associated neurological disease. To characterize TCR repertoire, CD8+ lymphocytes from peripheral blood were cloned in limiting dilution, and the resulting wells were screened for HTLV-I-specific precursor CTL activity. RNA was isolated from HLA-A2 restricted HTLV-I tax peptide-specific (tax 11-19; LLFGYPVYV) CD8+ CTL lines and cDNA was analyzed by PCR amplification using V alpha and V beta chain family-specific oligonucleotide primers. The results indicate that CD8+ cytotoxic T cell lines from HLA-A2 HAM/TSP patients express a limited repertoire of T cell receptor chains which may correlate with duration and severity of disease. The restricted use of TCR genes expressed by antigen-specific CTL may play a critical role in the pathogenesis of HAM/TSP and may be of value in developing immunotherapeutic strategies that focus on eliminating these cells or inhibiting their activity.
从患有人类嗜T淋巴细胞病毒I型（HTLV-I）相关神经疾病患者的外周血淋巴细胞中，确定了HTLV-I反式激活蛋白（tax）特异性、HLA I类分子限制性CD8+细胞毒性T细胞（CTL）的T细胞受体（TCR）Vα和Vβ链的使用情况。为了表征TCR库，对来自外周血的CD8+淋巴细胞进行有限稀释克隆，并对所得孔进行HTLV-I特异性前体CTL活性筛选。从HLA-A2限制性HTLV-I tax肽特异性（tax 11-19；LLFGYPVYV）CD8+CTL系中分离RNA，并用Vα和Vβ链家族特异性寡核苷酸引物通过PCR扩增分析cDNA。结果表明，来自HLA-A2 HTLV-I相关脊髓病/热带痉挛性截瘫（HAM/TSP）患者的CD8+细胞毒性T细胞系表达有限的T细胞受体链库，这可能与疾病的持续时间和严重程度相关。抗原特异性CTL表达的TCR基因的限制性使用可能在HAM/TSP的发病机制中起关键作用，并且在开发侧重于消除这些细胞或抑制其活性的免疫治疗策略中可能具有价值。
