Division of Experimental Medicine, Department of Medicine, University of California San Francisco, San Francisco, California, United States of America.
PLoS Negl Trop Dis. 2011 Apr 26;5(4):e1030. doi: 10.1371/journal.pntd.0001030.
The T cell immunoglobulin mucin 3 (Tim-3) receptor is highly expressed on HIV-1-specific T cells, rendering them partially "exhausted" and unable to contribute to the effective immune mediated control of viral replication. To elucidate novel mechanisms contributing to the HTLV-1 neurological complex and its classic neurological presentation called HAM/TSP (HTLV-1 associated myelopathy/tropical spastic paraparesis), we investigated the expression of the Tim-3 receptor on CD8(+) T cells from a cohort of HTLV-1 seropositive asymptomatic and symptomatic patients. Patients diagnosed with HAM/TSP down-regulated Tim-3 expression on both CD8(+) and CD4(+) T cells compared to asymptomatic patients and HTLV-1 seronegative controls. HTLV-1 Tax-specific, HLA-A*02 restricted CD8(+) T cells among HAM/TSP individuals expressed markedly lower levels of Tim-3. We observed Tax expressing cells in both Tim-3(+) and Tim-3(-) fractions. Taken together, these data indicate that there is a systematic downregulation of Tim-3 levels on T cells in HTLV-1 infection, sustaining a profoundly highly active population of potentially pathogenic T cells that may allow for the development of HTLV-1 complications.
T 细胞免疫球蛋白黏蛋白 3（Tim-3）受体在 HIV-1 特异性 T 细胞上高度表达，使它们部分“耗尽”，无法为有效免疫介导的病毒复制控制做出贡献。为了阐明有助于 HTLV-1 神经系统复合物及其经典神经系统表现（HTLV-1 相关脊髓病/热带痉挛性截瘫，HAM/TSP）的新机制，我们研究了来自 HTLV-1 血清阳性无症状和有症状患者队列的 CD8(+) T 细胞上 Tim-3 受体的表达。与无症状患者和 HTLV-1 血清阴性对照相比，诊断为 HAM/TSP 的患者下调了 CD8(+)和 CD4(+) T 细胞上的 Tim-3 表达。在 HAM/TSP 个体中，HTLV-1 Tax 特异性、HLA-A*02 限制的 CD8(+) T 细胞表达明显更低水平的 Tim-3。我们观察到 Tax 在 Tim-3(+)和 Tim-3(-) 两个部分都有表达细胞。总之，这些数据表明，在 HTLV-1 感染中，T 细胞上 Tim-3 水平存在系统性下调，维持了一群潜在致病性 T 细胞的高度活跃，这可能允许 HTLV-1 并发症的发展。
