Phenotypically and functionally distinct subsets contribute to the expansion of CD56-/CD16+ natural killer cells in HIV infection
Phenotypically and functionally distinct subsets contribute to the expansion of CD56-/CD16+ natural killer cells in HIV infection
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DOI：
10.1097/qad.0b013e32833b556f
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发表时间：
2010-07-31
期刊：
影响因子：
3.8
通讯作者：
Meyer-Olson, Dirk
中科院分区：
文献类型：
--
作者：
Hong, Henoch S.;Eberhard, Johanna M.;Meyer-Olson, Dirk
目的：人类免疫缺陷病毒(HIV)慢性感染与自然杀伤(NK)细胞激活和周转增加以及NK细胞内平衡紊乱有关，包括CD56(+)NK细胞丢失和CD56(-)/CD16(+)NK细胞功能紊乱。设计：对34例未经治疗的HIV感染者和15例血清阴性患者的CD56(-)/CD16(+)NK细胞进行横断面研究。方法：采用流式细胞术分析NK细胞。结果：CD56(-)/CD16(+)NK细胞是一种异质性细胞，由CD122(-)/CCR7(+)细胞和CD122(+)/CCR7(-)细胞组成。我们发现，在HIV血清阳性个体中，扩增的CD122(+)而不是CCR7(+)细胞具有类似于CD56(Dim)/CD16(+)NK细胞的衰老标记CD57的表达以及KIRS、CD8、穿孔素和颗粒酶B的表达，尽管CD57表达穿孔素和颗粒酶B，但CD57表达的细胞在CD107a检测中脱颗粒细胞数量较少，表明其功能受损。但总CD56(-)/CD16(+)NK细胞及其不同亚群的扩增与病毒载量和CD4细胞计数之间无相关性。结论：CD56(-)/CD16(+)细胞在HIV感染中的扩增是由该人群中高表达终末分化标志的亚群驱动的，其表型类似于CD56(Dim)/CD16(+)NK细胞。(C)2010年Wolters Kluwer Health垂直酒吧Lippincott Williams&Wilkins
Objective: Chronic HIV infection has been associated with activation and increased turnover of natural killer (NK) cells as well as with disturbed homeostasis of the NK cell compartment, including loss of CD56(+) NK cells and accumulation of dysfunctional CD56(-)/CD16(+) NK cells. We performed a comprehensive phenotypical and functional characterization of this population.Design: A cross-sectional study was performed to analyze CD56(-)/CD16(+) NK cells from 34 untreated HIV-infected and 15 seronegative individuals.Methods: NK cells were analyzed by flow cytometry. Degranulation was assessed by measuring their expression of CD107a after stimulation with K562 cells, interleukin-12 and interleukin-15.Results: CD56(-)/CD16(+) NK cells are heterogeneous and composed of two populations, namely CD122(-)/CCR7(+) cells and CD122(+)/CCR7(-) cells. We show that expanded CD122(+) but not CCR7(+) cells in HIV-seropositive individuals are characterized by expression of senescence marker CD57 similarly to CD56(dim)/CD16(+) NK cells along with expression of KIRs, CD8, perforin and granzyme B. Despite expression of perforin and granzyme B, CD57 expressing cells exhibited less numbers of degranulating cells as measured by CD107a, indicating their functional impairment. However, there was no correlation between expansion of total CD56(-)/CD16(+) NK cells or the distinct subpopulations and viral load or CD4 cell count. Conclusion: These data indicate that expansion of CD56(-)/CD16(+) cells in HIV infection is driven by a distinct subset within this population with high expression of terminal differentiation marker with a phenotype resembling CD56(dim)/CD16(+) NK cells. (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins