Age-related changes in the content of αβ-, γδ-T-lymphocytes and some its minor subpopulations in healthy children

Abstract

Introduction. Determination of the qualitative and quantitative content of cells of the immune system in healthy children is important for the formation of normal cell’s parameters, which is necessary both for research purposes and for clinical use. Data on the quantitative content of αβ-, γδ-T-lymphocytes and, especially, its minor subpopulations in children of different age groups are limited and extremely contradictory, so there is a need for such studies.

Aim of the study – to search the relative and absolute content of lymphocytes, Т-lymphocytes, αβ- and γδ-Т-lymphocytes, minor subpopulations: double negative and double positive T cells (DNT- and DPT-cells) in the peripheral blood of healthy children of different ages and to assess the correlation between the studied parameters and the age of children.

Material and methods. The venous blood samples of 83 healthy children (boys and girls), aged from 7 months to 14 years, was carried out. Monoclonal antibodies conjugated with various fluorochromes were used to detect the content of lymphocytes and its subpopulations. Determination of the number and percentage of lymphocytes and its subpopulations was carried out by flow cytometry.

Results. A decrease in the absolute number of γδ-T-killers in the blood of older children was found. The content of γδ-Т-lymphocytes, DNT- and DPT-cells remained stable in all age groups.

Conclusion. The decrease in the percentage of lymphocytes in healthy children depends on age. The absolute number of lymphocytes, T-lymphocytes, αβ-T cells and γδ-T-killers progressively decreases with age, while the number of γδ-T-lymphocytes, γδ-T-helpers, DPT- and DNT-cells remains unchanged.

Keywords:T cells; αβ-T-lymphocytes; γδ-Т-lymphocytes; healthy children; minor subpopulations; flow cytometry

For citation: Bogomyagkova E.N., Solpov A.V., Tereshkov P.P., Trushina N.G., Vitkovsky Yu.A. Age-related changes in the content of αβ-, γδ-Т-lymphocytes and some its minor subpopulations in healthy children. Immunologiya. 2021; 42 (5): 526–35. DOI: https://doi.org/10.33029/0206-4952-2021-42-4-526-535 (in Russian)

Funding. The study had no sponsor support.

Conflict of interests. Authors declare no conflict of interests.

References

1. Tosato F., Bucciol G., Pantano G., Putti M.C., Sanzari M.C., Basso G., Plebani M. Lymphocytes subsets reference values in childhood. Cytometry A. 2015; 87 (1): 81–5. DOI: https://doi.org/10.1002/cyto.a.22520

2. Valiathan R., Ashman M., Asthana D. Effects of Ageing on the Immune System: Infants to Elderly. Scand J Immunol. 2016; 83 (4): 255–66. DOI: https://doi.org/10.1111/sji.12413

3. Mandala W.L., Ananworanich J., Apornpong T., Kerr S.J., MacLennan J.M., Hanson C., Jaimulwong T., Gondwe E.N., Rosenblatt H.M., Bunupuradah T., Molyneux M.E., Spector S.A., Pancharoen C., Gelman R.S., MacLennan C.A., Shearer W.T. Control lymphocyte subsets: can one country's values serve for another's? J Allergy ClinImmunol. 2014; 134 (3): 759–61.e8. DOI: https://doi.org/10.1016/j.jaci.2014.06.030

4. Kumar B.V., Connors T., Farber D.L. Human T cell development, localization, and function throughout life. Immunity. 2018; 48 (2): 202–13. DOI: https://doi.org/10.1016/j.immuni.2018.01.007

5. Hwang J.R., Byeon Y., Kim D., Park S.G. Recent insights of T cell receptor-mediated signaling pathways for T cell activation and development. Experimental & Molecular Medicine. 2020; 52: 750–61. DOI: https://doi.org/10.1038/s12276-020-0435-8

6. Muro R., Takayanagi H., Nitta T. T cell receptor signaling for γδTcell. Inflammation and Regeneration. 2019; 39: 6. DOI: https://doi.org/10.1186/s41232-019-0095-z

7. Gaud G., Lesourne R., Love P.E. Regulatory mechanisms in T cell receptor signalling. Nat Rev Immunol. 2018; (8): 485–97. DOI: https://www.doi.org/10.1038/s41577-018-0020-8

8. Vermijden D., Gatti D., Kouzeli A., Rus T., Eberl M. T cell responses: How many ligands will it take till we know? Semin Cell Dev Biol. 2018; 84: 75–86. DOI: https://www.doi.org/10.1016/j.semcdb.2017.10.009

9. Solpova O.A. Participation of TCRαβ and γδT-lymphocytes, P-selectin in the formation of cell-platelet coaggregates. ENI Zabaikalsky Medical Bulletin. 2016; 2: 71–9. (in Russian)

10. Benveniste P.M., Roy S., Nakatsugawa M., Chen E.L.Y., Nguyen L., Millar D.G., Ohashi P.S., Hirano N., Adams E.J., Zúñiga-Pflücker J.C. Generation and molecular recognition of melanoma-associated antigen-specific human γδ T cells. Sci Immunol. 2018; 3 (30): eaav4036. DOI: https://www.doi.org/10.1126/sciimmunol.aav4036

11. Guo X.J., Dash P., Crawford J.C., Allen E.K., Zamora A.E., Boyd D.F., Duan S., Bajracharya R., Awad W.A., Apiwattanakul N., Vogel P., Kanneganti T.D., Thomas P.G. Lung γδ T Cells Mediate Protective Responses during Neonatal Influenza Infection that Are Associated with Type 2 Immunity. Immunity. 2018; 49 (3): 531–44.e6. DOI: https://www.doi.org/10.1016/j.immuni.2018.07.011

12. Lawand M., Déchanet-Merville J., Dieu-Nosjean M.-C. Key features of gamma-delta T-cell subsets in human diseases and their immunotherapeutic implications. Front. Immunol. 2017. DOI: https://doi.org/10.3389/fimmu.2017.00761

13. Tian D., Yang L., Wang S., et al. Double negative T cells mediate Lag3-dependent antigen-specific protection in allergic asthma. Nat Commun. 2019; 10: 4246. DOI: https://doi.org/10.1038/s41467-019-12243-0

14. Haug T., Aigner M., Peuser M.M., Strobl C.D., Hildner K., Mougiakakos D., Bruns H., Mackensen A., Völkl S. Human Double-Negative Regulatory T-Cells Induce a Metabolic and Functional Switch in Effector T-Cells by Suppressing mTOR Activity. Front Immunol. 2019; 10: 883. DOI: https://www.doi.org/10.3389/fimmu.2019.00883

15. Lerkvaleekul B., Apiwattanakul N., Klinmalai C., Hongeng S., Vilaiyuk S. Age-related changes in lymphocyte subpopulations in healthy Thai children. J Clin Lab Anal. 2020; 34 (5): e23156. DOI: https://www.doi.org/10.1002/jcla.23156

16. Liapis K., Tsagarakis N.J., Panitsas F., Taparkou A., Liapis I., Roubakis C., Tsokanas D., Vasileiou P., Grigoriou E., Kakiopoulos G., Psarra K., Farmaki E., Paterakis G. Causes of double-negative T-cell lymphocytosis in children and adults. J Clin Pathol. 2020; 73 (7):431–8. DOI: https://www.doi.org/10.1136/jclinpath-2019-206255

17. Li H., Adamopoulos I.E., Moulton V.R., Stillman I.E., Herbert Z., Moon J.J., Sharabi A., Krishfield S., Tsokos M.G., Tsokos G.C. Systemic lupus erythematosus favors the generation of IL-17 producing double negative T cells. Nat Commun. 2020; 11 (1): 2859. DOI: https://www.doi.org/10.1038/s41467-020-16636-4

18. Alexander J.J., Jacob A., Chang A., Quigg R.J., Jarvis J.N. Double negative T cells, a potential biomarker for systemic lupus erythematosus. Precis Clin Med. 2020; 3 (1): 34–43. DOI: https://www.doi.org/10.1093/pcmedi/pbaa001

19. Brandt D., Hedrich C.M. TCRαβ+CD3+CD4-CD8- (double negative) T cells in autoimmunity. Autoimmunity Reviews. 2018; 17 (4): 422–30. DOI: https://www.doi.org/10.1016/j.autrev.2018.02.001

20. Overgaard N.H., Jung J.W., Steptoe R.J., Wells J.W. CD4+/CD8+ double-positive T cells: more than just a developmental stage? J Leukoc Biol. 2015; 97 (1): 31–8. DOI: https://www.doi.org/10.1189/jlb.1RU0814-382

21. Bohner P., Chevalier M.F., Cesson V., Rodrigues-Dias S.C., Dartiguenave F., Burruni R., Tawadros T., Valerio M., Lucca I., Nardelli-Haefliger D., Jichlinski P., Derré L. Double positive CD4+CD8+ T cells are enriched in urological cancers and favor T helper-2 polarization. Front Immunol. 2019; 10: 622. DOI: https://www.doi.org/10.3389/fimmu.2019.00622

22. Parrot T., Gorin J.B., Ponzetta A., Maleki K.T., Kammann T., Emgård J., Perez-Potti A., Sekine T., Rivera-Ballesteros O.; Karolinska COVID-19 Study Group, Gredmark-Russ S., Rooyackers O., Folkesson E., Eriksson L.I., Norrby-Teglund A., Ljunggren H.G., Björkström N.K., Aleman S., Buggert M., Klingström J., Strålin K., Sandberg J.K. MAIT cell activation and dynamics associated with COVID-19 disease severity. Sci Immunol. 2020; 5 (51): eabe1670. DOI: https://www.doi.org/10.1126/sciimmunol.abe1670

23. Khaidukov S.V., Baidun L.A., Zurochka A.V., Totolyan Areg A. Standardized technology «study of the subpopulation composition of peripheral blood lymphocytes using flow cytofluorimeters-analyzers» (project). Medical immunology. 2012; 14 (3): 255–68. (in Russian)

24. Marchant A., Kollmann T.R. Understanding the ontogeny of the immune system to promote immune-mediated health for life. FrontImmunol. 2015; 6: 77. DOI: https://www.doi.org/10.3389/fimmu.2015.00077

25. Kollmann T.R., Kampmann B., Mazmanian S.K., Marchant A., Levy O. Protecting the newborn and young infant from infectious diseases: lessons from immune ontogeny. Immunity. 2017; 46 (3): 350–63. DOI: https://www.doi.org/10.1016/j.immuni.2017.03.009

26. Semmes E.C., Chen J.-L., Goswamil R., Burt T.D., Permar S.R., Fouda G.G. Understanding early-life adaptive immunity to guide interventions for pediatric health front. Immunol. 2021. DOI: https://doi.org/10.3389/fimmu.2020.595297

27. Parker M.E., Ciofani M. Regulation of γδ T Cell Effector Diversification in the Thymus. FrontImmunol. 2020; 11: 42. DOI: https://www.doi.org/10.3389/fimmu.2020.00042

28. Matthew A. Fischer Natasha B. Golovchenko Karen L. Edelblum γδ T cell migration: Separating trafficking from surveillance behaviors at barrier surfaces. 2020. DOI: https://doi.org/10.1111/imr.12915

29. Dimova T., Brouwer M., Gosselin F., Tassignon J., Leo O., Donner C., Marchant A., Vermijlen D. Effector Vγ9Vδ2 T cells dominate the human fetal γδ T-cell repertoire. Proc Natl AcadSci USA. 2015; 112 (6): E556–65. DOI: https://www.doi.org/10.1073/pnas.1412058112

30. Clark B.L., Thomas P.G. A Cell for the ages: human γδ T cells across the lifespan. Int J MolSci. 2020; 21 (23): 8903. DOI: https://www.doi.org/10.3390/ijms21238903

31. Xu W., Lau Z.W.X., Fulop T., Larbi A. The Aging of γδ T Cells. Cells. 2020; 9 (5): 1181. DOI: https://doi.org/10.3390/cells9051181

32. D'Acquisto F., Crompton T. CD3+CD4-CD8- (double negative) T cells: saviours or villains of the immune response? Biochem Pharmacol. 2011; 82 (4): 333–40. DOI: https://www.doi.org/10.1016/j.bcp.2011.05.019

33. Ding Y., Zhou L., Xia Yu., Song H., Yang J., Zhao X. Reference values for peripheral blood lymphocyte subsets of healthy children in China. Journal of allergology and clinical immunology. 2018. DOI: https://doi.org/10.1016/j.jaci.2018.04.022

34. Valiathan R., Ashman M., Asthana D. Effects of Ageing on the Immune System: Infants to Elderly. Scand J Immunol. 2016; 83 (4): 255–66. DOI: https://www.doi.org/10.1111/sji.12413

35. Khaidukov S.V. Small subpopulations of T-helpers (Th naive thymic, Th naive central, Th9, Th22 and CD4+CD8+ double positive T cells. Medical Immunology. 2013; 15 (6): 503–12. (in Russian)

36. Khaidukov S.V., Baidun L.V. Modern approaches to assessing the cellular component of the immune status. Medical alphabet. 2015; 2 (8): 44–51. (in Russian)

37. Zhirkov A.A., Alekseeva L.A., Zheleznikova G.F., Skripchenko N.V., Monakhova N.E., Bessonova T.V. Major and minor subpopulations of blood and cerebrospinal fluid lymphocytes in children with meningitis. Infection and immunity. 2021; 11 (1): 111–22. (in Russian)

38. Suprun E.N. The state of the immune system at different age periods. Allergology and Immunology in Pediatrics. 2013; 4 (35): 31–6. (in Russian)

All articles in our journal are distributed under the Creative Commons Attribution 4.0 International License (CC BY 4.0 license)


JOURNALS of «GEOTAR-Media»