Parker C E, Daenke S, Nightingale S, Bangham C R
Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, United Kingdom.
Virology. 1992 Jun;188(2):628-36. doi: 10.1016/0042-6822(92)90517-s.
In human T cell lymphoma/leukemia virus (HTLV-1)-infected people with tropical spastic paraparesis (TSP), there are activated HTLV-1-specific cytotoxic T lymphocytes (CTL) in the circulation and lymphocytic infiltrates in spinal cord lesions that are rich in CD8+ T cells. These observations suggest a role for virus-specific CTL in the pathogenesis of TSP. We have examined the anti-HTLV-1 cytotoxic activity of freshly isolated CD8+ T cells from peripheral blood lymphocytes of eight subjects seropositive for HTLV-1. Four of five subjects with TSP had circulating activated anti-Tax CTL. However, two of three seropositive subjects without TSP also had activated anti-Tax CTL. These observations show that such activated CTL are not confined to patients with TSP and raise some uncertainty about their significance in the pathogenesis of the disease. In cultures of CD8+ T cells from two TSP subjects, we detected CTL with other HTLV-1 specificities, without exogenous antigenic stimulation. A CTL epitope in the middle region of Tax and one in the C terminus of Pol have been mapped at the peptide level and the HLA Class 1 molecules restricting their recognition have been defined.
在感染人类T细胞淋巴瘤/白血病病毒1型(HTLV-1)并患有热带痉挛性截瘫(TSP)的患者中,循环系统中存在活化的HTLV-1特异性细胞毒性T淋巴细胞(CTL),脊髓病变处有富含CD8+T细胞的淋巴细胞浸润。这些观察结果提示病毒特异性CTL在TSP发病机制中发挥作用。我们检测了8名HTLV-1血清阳性受试者外周血淋巴细胞中新鲜分离的CD8+T细胞的抗HTLV-1细胞毒性活性。5名TSP患者中有4名循环中有活化的抗Tax CTL。然而,3名无TSP的血清阳性受试者中有2名也有活化的抗Tax CTL。这些观察结果表明,此类活化的CTL并非TSP患者所特有,这也增加了其在该疾病发病机制中的意义的不确定性。在来自2名TSP受试者的CD8+T细胞培养物中,我们在无外源性抗原刺激的情况下检测到具有其他HTLV-1特异性的CTL。已在肽水平上定位了Tax中间区域的一个CTL表位和Pol C末端的一个CTL表位,并确定了限制其识别的HLA I类分子。