Reduced Tim-3 Expression on Human T-lymphotropic Virus Type I (HTLV-I) Tax-specific Cytotoxic T Lymphocytes in HTLV-I Infection
Reduced Tim-3 Expression on Human T-lymphotropic Virus Type I (HTLV-I) Tax-specific Cytotoxic T Lymphocytes in HTLV-I Infection
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DOI：
10.1093/infdis/jiq153
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发表时间：
2011-04-01
影响因子：
6.4
通讯作者：
Kubota, Ryuji
中科院分区：
文献类型：
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作者：
Abdelbary, Nashwa H.;Abdullah, Hazem M.;Kubota, Ryuji
T细胞免疫球蛋白和粘蛋白结构域包含分子-3(Tim-3)和程序性细胞死亡-1(PD-1)是T细胞耗竭分子。我们研究了TIM-3和PD-1在人T淋巴细胞病毒I型(HTLV-I)感染中的表达。与健康对照组相比，HTLV-I相关性脊髓病/热带痉挛截瘫(HAM/TSP)患者和HTLV-I携带者的CD4(+)和CD8(+)T细胞TIM-3表达降低，而PD-1表达无明显变化。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(+)，税务特异性CTL产生较少的干扰素-γ，表现出较低的细胞杀伤活性。然而，我们没有观察到HAM/TSP患者和携带者的Tax特异性CTL之间TIM-3的表达或细胞溶解活性的差异。此外，HTLV-I感染的CD4(+)T细胞TIM-3表达降低。这些数据表明，在HTLV-I感染中，TIM-3的表达减少，大量的TIM-3(-)HTLV-I特异性CTL保留了它们的杀细胞活性，从而控制了病毒的复制。
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-gamma 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.