Severe loss of invariant NKT cells exhibiting anti-HTLV-1 activity in patients with HTLV-1-associated disorders
Severe loss of invariant NKT cells exhibiting anti-HTLV-1 activity in patients with HTLV-1-associated disorders
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DOI：
10.1182/blood-2009-02-203042
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发表时间：
2009-10-08
期刊：
影响因子：
20.3
通讯作者：
Yamano, Yoshihisa
中科院分区：
文献类型：
--
作者：
Azakami, Kazuko;Sato, Tomoo;Yamano, Yoshihisa
不变的自然杀伤T（iNKT）细胞是调节对微生物，癌症和自身免疫的免疫反应的独特T细胞。我们评估了感染人类嗜T淋巴细胞病毒1型（HTLV-1）的人的iNKT细胞的特征。尽管大多数感染者在其一生中保持无症状携带者（AC），但一小部分通常具有高平衡前病毒载量，发展为2种疾病：HTLV-1相关性脊髓病/热带痉挛性下肢轻瘫（HAM/TSP）和成人T细胞白血病（ATL）。我们证明了HAM/TSP和ATL患者外周血中iNKT、NK和树突状细胞的频率降低。我们还观察到感染者外周血中iNKT细胞频率与HTLV-1前病毒载量之间呈负相关。值得注意的是，用α-半乳糖神经酰胺体外刺激外周血细胞导致来自AC而不是HAM/TSP或ATL患者的样品中iNKT细胞数量增加，随后HTLV-1感染的T细胞数量减少。我们的研究结果表明，iNKT细胞有助于对HTLV-1的免疫防御，并且iNKT细胞耗竭在HAM/TSP和ATL的发病机制中起重要作用。因此，基于iNKT细胞的免疫疗法可能是预防这些HTLV-1相关疾病的有效策略。（血。2009; 114：3208-3215）
Invariant natural killer T (iNKT) cells are unique T cells that regulate the immune response to microbes, cancers, and autoimmunity. We assessed the characteristics of iNKT cells from persons infected with human T-lymphotropic virus type 1 (HTLV-1). Whereas most infected persons remain asymptomatic carriers (ACs) throughout their lives, a small proportion, usually with high equilibrium proviral loads, develop 2 diseases: HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia (ATL). We demonstrated that the frequency of iNKT, NK, and dendritic cells in the peripheral blood of HAM/TSP and ATL patients is decreased. We also observed an inverse correlation between the iNKT cell frequency and the HTLV-1 proviral load in the peripheral blood of infected persons. Notably, in vitro stimulation of peripheral blood cells with alpha-galactosylceramide led to an increase in the iNKT cell number and a subsequent decrease in the HTLV-1-infected T-cell number in samples from ACs but not HAM/TSP or ATL patients. Our results suggest that iNKT cells contribute to the immune defense against HTLV-1, and iNKT-cell depletion plays an important role in the pathogenesis of HAM/TSP and ATL. Therefore, iNKT cell-based immunotherapy may be an effective strategy for preventing these HTLV-1-associated disorders. (Blood. 2009; 114: 3208-3215)