Progress on the Distribution of NK Cells in Healthy Human Peripheral Blood

© 2025 by the Authors. Licensee Whioce Publishing, Singapore. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC BY-NC 4.0) ( https://creativecommons.org/licenses/by-nc/4.0/ )

Download PDF

Cite

XML

HTML

Abstract

NK cells are an important subset of lymphocytes in the human immune system and play a key role in antiviral and anti-tumor immunity. In this paper, the distribution characteristics and dynamic changes of peripheral blood NK cells in healthy people were systematically reviewed, focusing on the influence of age, gender, ethnicity, and environmental factors. Studies have shown that NK cells show a relatively stable distribution ratio in healthy adults, while in the development stage of children, they show dynamic characteristics that increase with age. The receptor expression and function of NK cells in the elderly population showed an age-related downward trend, indicating that the quality of NK cells, rather than the quantity, was a key indicator of age-related immune changes. Different ethnic groups and high-altitude environments also had a significant impact on NK cell distribution. This paper not only summarizes the quantitative characteristics of NK cell distribution but also analyzes the mechanism of its functional phenotypic changes, provides a scientific basis for clinical immune assessment, and points out the direction for future basic research and clinical application of NK cells.

References

Björkström NK, Strunz B, Ljunggren HG, Natural Killer Cells in Antiviral Immunity. Nat Rev Immunol, 2022, 22(2): 112–123.

Ding Y, Zhou L, Xia Y, et al., 2018, Reference Values for Peripheral Blood Lymphocyte Subsets of Healthy Children in China. J Allergy Clin Immunol, 142 (3): 970–973.

Meng X, Shi Y, Li S, et al., 2020, Establishment of Reference Interval for Lymphocyte Subsets in Healthy Children in Henan. Jiangsu Preventive Medicine, 31(1): 39–43.

Wang W, Mao B, Wang J, et al., 2019, Flow Cytometry to Establish the Normal Reference Value Range for the Relative Count of Peripheral Blood Lymphocyte Subsets in Preschool Han Children in Gansu Province. Journal of Evidence-Based Pediatrics, 14(3): 181–183.

Lin S, Gao H, Li J, et al., 2016, Establishment of Normal Reference Range for Peripheral Blood Lymphocyte Subsets and Main Activation-Related Indicators in Healthy Children in Fuzhou. Experimental and Laboratory Medicine, 34(3): 298–303.

Björkström NK, Ljunggren HG, Michaëlsson J, 2016, Emerging Insights into Natural Killer Cells in Human Peripheral Tissues. Nat. Rev. Immunol, 16: 310–320.

Zhou J, Gu S, Peng H, et al., 2012, Detection of Peripheral Blood Lymphocyte Subsets in Tibetan and Han Populations at an Altitude of 4500m. Journal of Immunology, 28(9): 820–822.

Wang P, Deng C, Huang X, et al., 2014, Distribution of Various T Cell Subsets and NK Cells in the Peripheral Blood of Healthy People of Different Ages and Genders in a Provincial Cancer Hospital. Journal of Qiqihar Medical College, 35(19): 2814–2816.

Kokuina E, Breff-Fonseca MC, Villegas-Valverde CA, et al., 2019, Normal Values of T, B and NK Lymphocyte Subpopulations in Peripheral Blood of Healthy Cuban Adults. MEDICC Rev, 21(2–3): 16–21.

Zhang L, Zhong H, Wei B, et al., 2022, Establishing Reference Values for Peripheral Blood Lymphocyte Subsets of Healthy Children in China Using a Single Platform. J Immunol Res, 2022: 5603566.

Du G, Ma Q, Yan H, et al., 2020, Establishment and Comparison Analysis of Reference Intervals for Peripheral Blood Lymphocyte Subsets of Tibetan and Han Children in Yushu Area, Qinghai Province. Journal of Clinical Laboratory, 38(7): 558–560.

Phan MT, Chun S, Kim SH, et al., 2017, Natural Killer Cell Subsets and Receptor Expression in Peripheral Blood Mononuclear Cells of a Healthy Korean Population: Reference Range, Influence of Age and Sex, and Correlation between NK cell Receptors and Cytotoxicity. Hum Immunol, 78 (2): 103–112.

Bisset LR, Lung TL, Kaelin M, et al., 2004, Reference Values for Peripheral Blood Lymphocyte Phenotypes Applicable to the Healthy Adult Population in Switzerland. Eur J Haematol, 72(3): 203–212.

Lakshmikanth T, Consiglio C, Sardh F, et al., 2024, Immune System Adaptation During Gender-Affirming Testosterone Treatment. Nature, 633(8028): 155–164.

Podhorzer A, Machicote A, Belén S, et al., 2018, Intrahepatic and Peripheral Blood Phenotypes of Natural Killer and T Cells: Differential Surface Expression of Killer Cell Immunoglobulin-Like Receptors. Immunology, 154(2): 261–273.

Rea IM, Maxwell LD, McNerlan SE, et al., 2013, Killer Immunoglobulin-like Receptors (KIR) haplogroups A and B track with Natural Killer Cells and Cytokine Profile in Aged Subjects: Observations from Octo/Nonagenarians in the Belfast Elderly Longitudinal Free-living Aging STudy (BELFAST) Immun Ageing, 10(1): 35.

Wienecke LM, Lemke LH, Fraccarollo D, et al., 2022, Altered Compositions of Monocyte, T Lymphocyte and NK Cell Subsets in Heart Failure of Adult Congenital Heart Disease. Int J Cardiol Congenit Heart Dis, 10: 100418.

Álvarez-Sánchez E, Carbayo Á, Valle-Tamayo N, et al., 2025, Single-Cell RNA Sequencing Highlights the Role of Distinct Natural Killer Subsets in Sporadic Amyotrophic Lateral Sclerosis. J Neuroinflammation, 22(1): 15.

Lamers-Kok N, Panella D, Georgoudaki AM, et al., 2022, Natural Killer Cells in Clinical Development as Non-Engineered, Engineered, and Combination Therapies. J Hematol Oncol, 15(1): 164.

Parisi S, Ruggeri L, Dan E, et al., 2021, Long-Term Outcome After Adoptive Immunotherapy With Natural Killer Cells: Alloreactive NK Cell Dose Still Matters. Front Immunol, 12: 804988.

Singh P, Szaraz-Szeles M, Mezei Z, et al., 2022, Age-Dependent Frequency of Unconventional T Cells in a Healthy Adult Caucasian Population: A Combinational Study of Invariant Natural Killer T Cells, γδ T Cells, and Mucosa-Associated Invariant T Cells. Geroscience, 44(4): 2047–2060.

Previous article in this issue

Next article in this issue