Division of Molecular Pathology, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, Japan.
J Infect Dis. 2011 Apr 1;203(7):948-59. doi: 10.1093/infdis/jiq153.
T cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3) and programmed cell death-1 (PD-1) are T cell exhaustion molecules. We investigated the expression of Tim-3 and PD-1 in human T-lymphotropic virus type I (HTLV-I) infection. Tim-3 expression, but not PD-1 expression, was reduced on CD4(+) and CD8(+) T cells of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients and HTLV-I carriers as compared with healthy controls. Tim-3 expression was also reduced in HTLV-I Tax-specific cytotoxic T lymphocytes (CTLs) as compared with cytomegalovirus-specific CTLs. Tim-3(+), but not PD-1(+), Tax-specific CTLs produced less interferon-γ and exhibited low cytolytic activity. However, we observed no difference in the expression of Tim-3 or cytolytic activity between Tax-specific CTLs of HAM/TSP patients or carriers. Moreover, HTLV-I-infected CD4(+) T cells showed decreased Tim-3 expression. These data suggest that Tim-3 expression is reduced in HTLV-I infection and that a high number of Tim-3(-) HTLV-I-specific CTLs preserves their cytolytic activity, thereby controlling viral replication.
T 细胞免疫球蛋白和黏蛋白结构域分子 3（Tim-3）和程序性细胞死亡蛋白 1（PD-1）是 T 细胞耗竭分子。我们研究了人类 T 淋巴细胞白血病病毒 I 型（HTLV-I）感染中 Tim-3 和 PD-1 的表达。与健康对照组相比，HTLV-I 相关脊髓病/热带痉挛性截瘫（HAM/TSP）患者和 HTLV-I 携带者的 CD4(+)和 CD8(+)T 细胞中 Tim-3 的表达降低，而 PD-1 的表达没有降低。与巨细胞病毒特异性 CTL 相比，HTLV-I Tax 特异性细胞毒性 T 淋巴细胞（CTL）中 Tim-3 的表达也降低。Tim-3(+)，而不是 PD-1(+)，Tax 特异性 CTL 产生较少的干扰素-γ，表现出低细胞溶解活性。然而，我们在 HAM/TSP 患者或携带者的 Tax 特异性 CTL 之间未观察到 Tim-3 表达或细胞溶解活性的差异。此外，HTLV-I 感染的 CD4(+)T 细胞显示出 Tim-3 表达降低。这些数据表明，Tim-3 的表达在 HTLV-I 感染中降低，大量的 Tim-3(-)HTLV-I 特异性 CTL 保持其细胞溶解活性，从而控制病毒复制。
