Suppression of R5-type of HIV-1 in CD4+ NKT cells by Vδ1+ T cells activated by flavonoid glycosides, hesperidin and linarin
Suppression of R5-type of HIV-1 in CD4+ NKT cells by Vδ1+ T cells activated by flavonoid glycosides, hesperidin and linarin
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DOI：
10.1038/s41598-019-40587-6
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发表时间：
2019-05
影响因子：
4.6
通讯作者：
Michiyuki Yonekawa;Masumi Shimizu;A. Kaneko;J. Matsumura;Hidemi Takahashi
中科院分区：
文献类型：
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作者：
Michiyuki Yonekawa;Masumi Shimizu;A. Kaneko;J. Matsumura;Hidemi Takahashi
我们利用缺乏tcr的Jurkat T细胞系J.RT3-T3.5建立了表达Vγ1和Vδ1 （1C116）或Vγ2和Vδ2 (2C21) T细胞受体（tcr）的转染物。这些γδ T细胞克隆分泌的IL-2的量准确地指示了tcr依赖性刺激。克隆2C21被先前报道的Vγ2Vδ2 (Vδ2)-TCR配体特异性刺激，如焦磷酸异戊酯（IPP）、乙胺或升塞膦酸盐。克隆1C116通过v - γ - 1v - δ1 (Vδ1)-TCR受到类黄酮苷（如橙皮苷和亚麻素）的强烈刺激，A环上有芦丁糖，B环上有甲氧基（-OCH3）取代。此外，橙皮苷和linarin对表达Vδ1-TCR的外周血单个核细胞（PBMC）来源的T细胞有刺激活性；这些活化的Vδ1+T细胞还分泌IL-5、IL-13、MIP-1α、MIP-1β和RANTES。橙皮苷和linarin刺激pbmc衍生的Vδ1+T细胞以剂量依赖性的方式抑制R5-HIV-1-NL（AD8）病毒在CD4+NKT细胞中的复制。据我们所知，这是第一次证明黄酮类苷激活功能性Vδ1+T细胞。
We established transfectants expressing T cell receptors (TCRs) either for Vγ1 and Vδ1 (1C116) or for Vγ2 and Vδ2 (2C21) using the TCR-deficient Jurkat T cell line J.RT3-T3.5. The amount of IL-2 secreted from these γδ T cell clones accurately indicated TCR-dependent stimulation. Clone 2C21 was specifically stimulated by previously reported ligands for Vγ2Vδ2 (Vδ2)-TCR such as isopentenyl pyrophospate (IPP), ethylamine, or risedronate. In contrast, clone 1C116 was strongly stimulated through the Vγ1Vδ1 (Vδ1)-TCR by flavonoid glycosides such as hesperidin and linarin, having both rutinose at the A ring and methoxy (-OCH3) substitution at the B ring. Additionally, hesperidin and linarin showed stimulatory activity for peripheral blood mononuclear cell (PBMC)-derived T cells expressing Vδ1-TCR; these activated Vδ1+T cells also secreted IL-5, IL-13, MIP-1α, MIP-1β and RANTES. Such PBMC-derived Vδ1+T cells stimulated by hesperidin and linarin suppressed R5-HIV-1-NL(AD8) viral replication in CD4+NKT cells in a dose-dependent manner. To the best of our knowledge, this is the first demonstration that flavonoid glycosides activate functional Vδ1+T cells.