Azakami Kazuko, Sato Tomoo, Araya Natsumi, Utsunomiya Atae, Kubota Ryuji, Suzuki Kenshi, Hasegawa Daisuke, Izumi Toshihiko, Fujita Hidetoshi, Aratani Satoko, Fujii Ryoji, Yagishita Naoko, Kamijuku Hajime, Kanekura Takuro, Seino Ken-ichiro, Nishioka Kusuki, Nakajima Toshihiro, Yamano Yoshihisa
Department of Molecular Medical Science, Institute of Medical Science, St Marianna University School of Medicine, Kawasaki, Japan.
Blood. 2009 Oct 8;114(15):3208-15. doi: 10.1182/blood-2009-02-203042. Epub 2009 Aug 7.
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.
不变自然杀伤T（iNKT）细胞是一类独特的T细胞，可调节对微生物、癌症和自身免疫的免疫反应。我们评估了感染1型人类嗜T淋巴细胞病毒（HTLV-1）者的iNKT细胞特征。大多数感染者终生保持无症状携带者（AC）状态，而一小部分人，通常前病毒载量处于高水平，会患上两种疾病：HTLV-1相关脊髓病/热带痉挛性截瘫（HAM/TSP）和成人T细胞白血病（ATL）。我们证明，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，会使AC样本中的iNKT细胞数量增加，随后HTLV-1感染的T细胞数量减少，但HAM/TSP或ATL患者的样本未出现这种情况。我们的结果表明，iNKT细胞有助于抵抗HTLV-1的免疫防御，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。
