Elovaara I, Koenig S, Brewah A Y, Woods R M, Lehky T, Jacobson S
Neuroimmunology Branch, National Institutes of Health, Bethesda, Maryland 20892.
J Exp Med. 1993 Jun 1;177(6):1567-73. doi: 10.1084/jem.177.6.1567.
The frequencies of human T cell lymphotropic virus type 1 (HTLV-1)-specific CD8+ precursor cytotoxic T lymphocytes (pCTL) were quantitated from lymphocytes obtained from the peripheral blood and cerebrospinal fluid (CSF) of infected individuals with and without HTLV-1-associated neurological disease. An estimate of the pCTL was obtained by separating CD8+ cells, plating these cells in limiting dilution, and testing wells for HTLV-1 specific lysis. Targets consisted of autologous lymphoblastoid cell lines (LCL) infected with vaccinia constructs expressing HTLV-1 gene products or LCL pulsed with HTLV-1 synthetic peptides. In patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), the frequency of HTLV-1 p40X-specific pCTL was at least 40-280-fold higher than in asymptomatic HTLV-1-infected individuals. All HAM/TSP patients (five of five) predominantly recognized HTLV-1 products encoded within the pX region. Lower pCTL to env were demonstrated in three patients, and only one of five HAM/TSP patients had pCTL to gag. A synthetic peptide corresponding to the tax region of HTLV-1 (peptide 11-19, amino acid sequence LLFGYPVYV) was recognized in association with human histocompatibility leukocyte antigen (HLA)-A2 in two HLA-A2 HAM/TSP patients with a high CD8+ pCTL frequency of 1/325 and 1/265, respectively. A second immunodominant region of HTLV-1 tax (peptide 90-55, amino acid sequence VPYKRIEEL) was identified to be restricted by HLA-B14 in two HLA-B14 HAM/TSP patients with a CD8+ pCTL frequency of 1/640 and 1/1,125, respectively. Lymphocytes from the CSF of a patient with HAM/TSP also showed a pCTL frequency against p40X of similar magnitude to that demonstrated from peripheral blood lymphocytes (PBL). The HLA-A2-mediated CSF pCTL activity to the immunodominant tax-specific peptide 11-19 was also comparable to pCTL from PBL. These results indicate that an extremely high pCTL frequency to HTLV-1 tax-encoded peptides may be related to pathogenesis of myeloneuropathy associated with HTLV-1.
从感染了人类嗜T淋巴细胞病毒1型（HTLV-1）且伴有或不伴有HTLV-1相关神经疾病的个体的外周血和脑脊液（CSF）中获取淋巴细胞，对HTLV-1特异性CD8⁺前体细胞毒性T淋巴细胞（pCTL）的频率进行定量分析。通过分离CD8⁺细胞、将这些细胞进行有限稀释铺板，并检测各孔的HTLV-1特异性裂解情况来估算pCTL。靶细胞包括感染了表达HTLV-1基因产物的痘苗构建体的自体淋巴母细胞系（LCL）或用HTLV-1合成肽脉冲处理的LCL。在患有HTLV-1相关脊髓病/热带痉挛性截瘫（HAM/TSP）的患者中，HTLV-1 p40X特异性pCTL的频率比无症状HTLV-1感染个体至少高40至280倍。所有HAM/TSP患者（5例中的5例）主要识别pX区域内编码的HTLV-1产物。3例患者中显示出针对env的较低pCTL水平，5例HAM/TSP患者中只有1例有针对gag的pCTL。在两名HLA-A2 HAM/TSP患者中，分别以1/325和1/265的高CD8⁺ pCTL频率识别了与人类组织相容性白细胞抗原（HLA）-A2相关的对应于HTLV-1 tax区域的合成肽（肽11-19，氨基酸序列LLFGYPVYV）。在两名HLA-B14 HAM/TSP患者中，分别以1/640和1/1125的CD8⁺ pCTL频率确定HTLV-1 tax的第二个免疫显性区域（肽90-55，氨基酸序列VPYKRIEEL）受HLA-B14限制。一名HAM/TSP患者脑脊液中的淋巴细胞对p40X的pCTL频率也显示出与外周血淋巴细胞（PBL）相似的幅度。HLA-A2介导的脑脊液对免疫显性tax特异性肽11-19的pCTL活性也与PBL中的pCTL相当。这些结果表明，针对HTLV-1 tax编码肽的极高pCTL频率可能与HTLV-1相关脊髓神经病的发病机制有关。
