Amand Mathieu, Iserentant Gilles, Poli Aurélie, Sleiman Marwan, Fievez Virginie, Sanchez Isaura Pilar, Sauvageot Nicolas, Michel Tatiana, Aouali Nasséra, Janji Bassam, Trujillo-Vargas Claudia Milena, Seguin-Devaux Carole, Zimmer Jacques
Department of Infection and Immunity, Luxembourg Institute of Health (LIH), Esch-sur-Alzette, Luxembourg.
Grupo de Inmunodeficiencias Primarias, Facultad de Medicina, Universidad de Antioquia UdeA, Medellín, Colombia.
Front Immunol. 2017 Jun 19;8:699. doi: 10.3389/fimmu.2017.00699. eCollection 2017.
Human natural killer (NK) cells can be subdivided in several subpopulations on the basis of the relative expression of the adhesion molecule CD56 and the activating receptor CD16. Whereas blood CD56CD16 NK cells are classically viewed as immature precursors and cytokine producers, the larger CD56CD16 subset is considered as the most cytotoxic one. In peripheral blood of healthy donors, we noticed the existence of a population of CD56CD16 NK cells that was frequently higher in number than the CD56 subsets and even expanded in occasional control donors but also in transporter associated with antigen processing-deficient patients, two familial hemophagocytic lymphohistiocytosis type II patients, and several common variable immunodeficiency patients. This population was detected but globally reduced in a longitudinal cohort of 18 HIV-1-infected individuals. Phenotypically, the new subset contained a high percentage of relatively immature cells, as reflected by a significantly stronger representation of NKG2A and CD57 cells compared to their CD56CD16 counterparts. The phenotype of the CD56CD16 population was differentially affected by HIV-1 infection as compared to the other NK cell subsets and only partly restored to normal by antiretroviral therapy. From the functional point of view, sorted CD56CD16 cells degranulated more than CD56CD16 cells but less than CD56CD16 NK cells. The population was also identified in various organs of immunodeficient mice with a human immune system ("humanized" mice) reconstituted from human cord blood stem cells. In conclusion, the CD56CD16 NK cell subpopulation displays distinct phenotypic and functional features. It remains to be clarified if these cells are the immediate precursors of the CD56CD16 subset or placed somewhere else in the NK cell differentiation and maturation pathway.
人类自然杀伤（NK）细胞可根据黏附分子CD56和激活受体CD16的相对表达情况细分为几个亚群。传统上认为血液中的CD56⁺CD16⁺NK细胞是未成熟的前体细胞和细胞因子产生者，而数量较多的CD56⁻CD16⁺亚群则被认为是细胞毒性最强的。在健康供体的外周血中，我们注意到存在一群CD56⁻CD16⁺NK细胞，其数量通常高于CD56⁺亚群，甚至在部分对照供体中有所扩增，在与抗原加工缺陷相关的转运体患者、两名家族性噬血细胞性淋巴组织细胞增生症II型患者以及几名常见变异型免疫缺陷患者中也出现了扩增。在一个由18名HIV-1感染者组成的纵向队列中检测到了这一群体，但总体数量有所减少。从表型上看，这个新亚群包含较高比例的相对未成熟细胞，这表现为与CD56⁺CD16⁺对应细胞相比，NKG2A和CD57细胞的比例显著更高。与其他NK细胞亚群相比，HIV-1感染对CD56⁻CD16⁺群体表型的影响有所不同，且抗逆转录病毒疗法仅使其部分恢复正常。从功能角度来看，分选后的CD56⁻CD16⁺细胞脱颗粒程度高于CD56⁺CD16⁺细胞，但低于CD56⁺CD16⁻NK细胞。在用人脐血干细胞重建了人类免疫系统的免疫缺陷小鼠（“人源化”小鼠）的各个器官中也鉴定出了这一群体。总之，CD56⁻CD16⁺NK细胞亚群具有独特的表型和功能特征。这些细胞是CD56⁺CD16⁺亚群的直接前体，还是处于NK细胞分化和成熟途径中的其他位置，仍有待阐明。
