北京大学学报(医学版) ›› 2024, Vol. 56 ›› Issue (5): 839-844. doi: 10.19723/j.issn.1671-167X.2024.05.014
Jiayi TIAN, Yixue GUO, Xia ZHANG, Xiaolin SUN, Jing HE*()
摘要:
目的: 研究中国健康人外周血中自然杀伤(natural killer,NK)细胞及其亚群的比例和数量,初步确定其正常值范围作为临床检验的参考数值。方法: 选取200例健康成年人,年龄范围为18~87岁,所有受试者被分成6个年龄组:18~30、31~40、41~50、51~60、61~70、71~87岁,收集外周血,以CD16、CD56、CD3、CD19等作为表面标记,使用流式细胞术检测NK细胞及亚群的相对比例及绝对计数。采用SPSS 27.0软件分析数据,计量资料用均数±标准差表示,同时进行t检验、方差分析或秩和检验比较各年龄组和性别组的差异,检验水准α=0.05,以P < 0.05为差异有统计学意义。结果: 200例健康成人受试者CD3-CD56+NK细胞的范围为(13.14±7.56)×106/L,CD56dimCD16+NK细胞的范围为(5.23±3.12)×106/L,CD56brightNK细胞的范围为(85.61±7.40)×106/L,NK T细胞的范围为(4.16±3.34)×106/L,NK B细胞的范围为(0.46±0.24)×106/L。CD3-CD56+NK和NK T细胞在和年龄的相关性方面差异无统计学意义(P=0.417,P=0.217);随着年龄的增长,NK B和CD56dimCD16+NK细胞的数量有一定的下降趋势(r=0.234,P < 0.001;r=0.099,P < 0.001),尤其是在50岁以后更加明显;CD56brightNK则随着年龄增长有上升趋势(r=0.143, P < 0.001)。结论: NK细胞及其亚群的检测对于自身免疫病、感染性疾病和肿瘤的诊断、治疗和预后分析具有重要参考价值;本研究为临床检测NK细胞亚群提供了初步的参考范围,但尚需扩大例数,进行多中心试验以进一步明确。
中图分类号:
1 | Yu J , Freud AG , Caligiuri MA . Location and cellular stages of natural killer cell development[J]. Trends Immunol, 2013, 34 (12): 573- 582. |
2 | Carrega P , Ferlazzo G . Natural killer cell distribution and trafficking in human tissues[J]. Front Immunol, 2012, 3, 347. |
3 | Zhu L , Karakizlis H , Weimer R , et al. Circulating NKG2A-NKG2D+ CD56dimCD16+ natural killer (NK) cells as mediators of functional immunosurveillance in kidney transplant recipients[J]. Ann Transplant, 2020, 25, e925162. |
4 | Marras F , Casabianca A , Bozzano F , et al. Control of the HIV-1 DNA reservoir is associated in vivo and in vitro with NKp46/NKp30 (CD335 CD337) inducibility and interferon gamma production by transcriptionally unique NK cells[J]. J Virol, 2017, 91 (23): e00647. |
5 | Cichocki F , Grzywacz B , Miller JS . Human NK cell development: One road or many?[J]. Front Immunol, 2019, 10, 2078. |
6 | Freud AG , Mundy-Bosse BL , Yu J , et al. The broad spectrum of human natural killer cell diversity[J]. Immunity, 2017, 47 (5): 820- 833. |
7 | Melzer S , Zachariae S , Bocsi J , et al. Reference intervals for leukocyte subsets in adults: Results from a population-based study using 10-color flow cytometry[J]. Cytometry B Clin Cytom, 2015, 88 (4): 270- 281. |
8 | Shu SA , Wang J , Tao MH , et al. Gene therapy for autoimmune disease[J]. Clin Rev Allergy Immunol, 2015, 49 (2): 163- 176. |
9 | Choi J , Lee SJ , Lee YA , et al. Reference values for peripheral blood lymphocyte subsets in a healthy korean population[J]. Immune Netw, 2014, 14 (6): 289- 295. |
10 | Yawata N , Selva KJ , Liu YC , et al. Dynamic change in natural killer cell type in the human ocular mucosa in situ as means of immune evasion by adenovirus infection[J]. Mucosal Immunol, 2016, 9 (1): 159- 170. |
11 | Tahrali I , Kucuksezer UC , Akdeniz N , et al. CD3-CD56+ NK cells display an inflammatory profile in RR-MS patients[J]. Immunol Lett, 2019, 216, 63- 69. |
12 | Bendelac A , Savage PB , Teyton L . The biology of NK T cells[J]. Annu Rev Immunol, 2007, 25, 297- 336. |
13 | McCarthy C , Shepherd D , Fleire S , et al. The length of lipids bound to human CD1d molecules modulates the affinity of NK T cell TCR and the threshold of NK T cell activation[J]. J Exp Med, 2007, 204 (5): 1131- 1144. |
14 | Simoni Y , Diana J , Ghazarian L , et al. Therapeutic manipulation of natural killer (NK) T cells in autoimmunity: Are we close to reality?[J]. Clin Exp Immunol, 2013, 171 (1): 8- 19. |
15 | Li M , Xiong Y , Li M , et al. Depletion but activation of CD56(dim)CD16(+)NK cells in acute infection with severe fever with thrombocytopenia syndrome virus[J]. Virol Sin, 2020, 35 (5): 588- 598. |
16 | Gayoso I , Sanchez-Correa B , Campos C , et al. Immunosene-scence of human natural killer cells[J]. J Innate Immun, 2011, 3 (4): 337- 343. |
17 | Solana R , Tarazona R , Gayoso I , et al. Innate immunosene-scence: Effect of aging on cells and receptors of the innate immune system in humans[J]. Semin Immunol, 2012, 24 (5): 331- 341. |
18 | Solana R , Pawelec G , Tarazona R . Aging and innate immunity[J]. Immunity, 2006, 24 (5): 491- 494. |
19 | Cunha CF , Ferraz-Nogueira R , Costa VFA , et al. Contribution of Leishmania braziliensis antigen-specific CD4+ T, CD8+ T, NK and CD3+CD56+NK T cells in the immunopathogenesis of cutaneous leishmaniasis patients: Cytotoxic, activation and exhaustion profiles[J]. PLoS One, 2020, 15 (3): e0229400. |
20 | Myers JA , Miller JS . Exploring the NK cell platform for cancer immunotherapy[J]. Nat Rev Clin Oncol, 2021, 18 (2): 85- 100. |
21 | Terrén I , Orrantia A , Vitallé J , et al. NK Cell metabolism and tumor microenvironment[J]. Frontiers in immunology, 2019, 10, 2278. |
22 | Zhang C , Liu Y . Targeting NK Cell Checkpoint receptors or molecules for cancer immunotherapy[J]. Front Immunol, 2020, 11, 1295. |
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