基础医学与临床 ›› 2017, Vol. 37 ›› Issue (7): 953-958.

• 研究论文 • 上一篇    下一篇

HIV-1早期感染者γδ T细胞对储藏库细胞的细胞毒作用

李珍,陆小凡,孙坚萍,粟斌,吴昊,张永宏,张彤   

  1. 首都医科大学附属北京佑安医院
  • 收稿日期:2017-04-11 修回日期:2017-05-17 出版日期:2017-07-05 发布日期:2017-06-23
  • 通讯作者: 张彤 E-mail:zt_doc@163.com
  • 基金资助:
    国家自然科学基金;北京市科技计划项目;北京市艾滋病重点实验室

Cytotoxic role of γδ T cells to latency cells in patients with early human immunodeficiency virus-1 infection

  • Received:2017-04-11 Revised:2017-05-17 Online:2017-07-05 Published:2017-06-23

摘要: 目的 探讨HIV-1早期感染者γδ T细胞是否具有清除HIV-1储藏库的能力。方法 入组HIV-1早期感染者16例,分离外周血单个核细胞,体外采用唑来膦酸(5 μmol/L)加IL-2(1 000 IU/mL)扩增γδ T细胞。乳酸脱氢酶(LDH)法检测γδ T细胞对储藏库细胞(J-Lat Full Length Clone10.6)的细胞毒作用;流式细胞计量术检测扩增前后γδ T细胞的表型和储藏库细胞中GFP的荧光强度。结果 唑来膦酸加IL-2在体外刺激γδ T细胞快速且大量扩增(P<0.001)。γδ T细胞对储藏库细胞具有较强的细胞毒作用,储藏库细胞中GFP的平均荧光强度显著减弱(P<0.05)。扩增后γδ T细胞表现出细胞毒性NK细胞样表型,HIV-1感染者CD56+Vδ2 T细胞的比例较健康对照显著增加(P<0.05)。结论 γδ T细胞具有清除HIV-1储藏库的能力,基于γδ T细胞的自体或异体过继免疫治疗有望成为清除储藏库,治愈HIV-1感染的一种新策略。

关键词: 人类免疫缺陷病毒-1, 储藏库, γδ T细胞, 细胞治疗

Abstract: Objective To investigate the cytotoxicity of γδ T cells to HIV-1 latency cell in patients with early HIV-1 infection. Methods Sixteen early HIV-1-infected patients were enrolled in this study. Peripheral blood mononuclear cells (PBMCs) of patients were isolated and γδ T cells were expanded using zoledronate (5 μmol/L) and interleukin (IL)-2 (1 000 IU/mL) ex vivo. Lactic dehydrogenase (LDH) was used to detect the cytotoxic role of γδ T cells to HIV-1 latency cell (J-Lat Full Length Clone10.6). The phenotype of γδ T cells before and after expansion and the intensity of GFP in HIV-1 latency cells were detected by flow cytometry. Results Zoledronate plus IL-2 stimulate rapid and large γδ T cells proliferation ex vivo (P<0.001). γδ T cells showed high cytotoxicity to latency cells, and the intensity of GFP in latency cells were decreased significantly (P<0.05). Moreover, expanded γδ T cells displayed cytotoxic NK-like phenotype, the frequency of CD56+Vδ2 T cells in patients with early HIV-1 infection was significant higher than that in healthy controls. Conclusions γδ T cell has an ability to eradicate HIV-1 latency, and γδ T cell-based autologous or xenogenous adoptive immunotherapy will be promising prospects to cure HIV-1 infection.

Key words: human immunodeficiency-1, latency, γδ T cell, immunotherapy

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