Clinical Investigation for Virus-Host Interactions and its Implication in the Development of HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP).

人类t细胞嗜淋巴病毒1型（HTLV-1）相关脊髓病/热带痉挛性麻痹（HAM/TSP）仅在HTLV-1感染个体的1-2%中观察到。我们之前报道HTLV-1 Tax亚型、几种HLA和非HLA基因与HAM/TSP的发生密切相关。基于这些发现，我们开发了最佳拟合逻辑回归方程来预测HAM/TSP的几率。我们将该方程应用于181名连续确定的健康HTLV-1携带者（hc），发现HAM/TSP的高几率与两个因素之间存在显著关联：活跃的髌骨深腱反射，这表明中枢神经系统存在潜在的损害，以及花细胞（ATL细胞）样异常淋巴细胞。我们的数据表明我们的方程对于检测亚临床HAM/ tsp相关的神经异常是有用的。我们进一步通过流式细胞术分析了HAM/TSP患者、hc和正常未感染对照的pbmc中的CD4+和CD8+ T细胞。我们使用由HLA及其免疫优势表位肽组成的合成四聚体直接从外周血中分析env特异性CD4+ T和tax特异性CD8+ T细胞。HAM/TSP患者中激活和克隆扩增的四聚体+CD4+和四聚体+CD8+ T细胞的频率明显高于hcc，提示慢性感染期间HTLV-1特异性T细胞的活跃和持续扩增在HAM/TSP的发展中起作用。

Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is observed only in 1-2% of HTLV-1 infected individuals. We have previously reported that HTLV-1 Tax subtype, several HLA and non-HLA genes are closely associated with the development of HAM/TSP. Based on these findings, we developed the best-fit logistic regression equation to predict the odds of HAM/TSP. We applied this equation to 181 consecutively ascertained healthy HTLV-1 carriers (HCs) and found a significant association between a high odds of HAM/TSP and two factors: brisk patellar deep tendon reflexes, which suggest latent central nervous system compromise, and flower cell (ATL cell)-like abnormal lymphocytes. Our data suggests the usefulness of our equation for detecting subclinical HAM/TSP-related neurological abnormalities. We further analyzed CD4+ and CD8+ T cells in PBMCs from HAM/TSP patients, HCs and normal uninfected controls by flow cytometry based analyses. We have used synthetic tetramers composed of HLA and its immunodominant epitope peptide to analyze Env-specific CD4+ T and Tax-specific CD8+ T cells directly from peripheral blood. Significantly higher frequency of activated and clonally expanded tetramer+CD4+ and tetramer+CD8+ T cells were observed in HAM/TSP patients than HCs, suggesting that active and continus expansion of HTLV-1 specific T cells during chronic infection play a role in the development of HAM/TSP.