HIV-1早期感染者γδT细胞对储藏库细胞的细胞毒作用  

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

作　　者：李珍[1,2] 陆小凡[1,2] 孙坚萍[3] 粟斌[1,2] 吴昊[1,2] 张永宏[3] 张彤[1,2] 

机构地区：[1]首都医科大学附属北京佑安医院感染中心,北京100069 [2]首都医科大学附属北京佑安医院北京市艾滋病研究重点实验室,北京100069 [3]首都医科大学附属北京佑安医院生物医学中心,北京100069

出　　处：《基础医学与临床》2017年第7期953-958,共6页Basic and Clinical Medicine

基　　金：国家自然科学基金青年基金(81501731);北京市艾滋病重点实验室项目(BZ0089);北京市科技计划项目(D141100000314005)

摘　　要：目的探讨HIV-1早期感染者γδT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,分离外周血单核细胞,体外采用唑来膦酸(5μmol/L)加IL-2(1 000 IU/m L)扩增γδT细胞。乳酸脱氢酶(LDH)法检测γδT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γδT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γδT细胞快速且大量扩增(P<0.001)。γδT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γδT细胞表现出细胞毒性NK细胞样表型,HIV-1感染者CD56+Vδ2T细胞的比例较健康对照显著增加(P<0.05)。结论γδT细胞具有清除HIV-1储藏库的能力,基于γδT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。Objective To investigate the cytotoxicity of γδ T cells to HIV- 1 latency cells 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 cells（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 stimulated rapid and large γδ T cells proliferation ex vivo （P〈0. 001 ）. γδ T ceils showed high cytotoxici- ty to latency cells, and the intensity of GFP in latency cells was 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- i infection was significantly higher than that of healthy controls. Conclusions γδ T cell has an ability to eradicate HIV- 1 latency, and γδT cell-based autologous or xenogenous adoptive immunotherapy will have promise prospects to cure HIV-1 infection.

关 键 词：人类免疫缺陷病毒-1 储藏库 ΓΔT细胞 细胞治疗 

分 类 号：R512.91[医药卫生—内科学]