TY - JOUR T1 - Establishing Age-Gender Specific Reference Values of T and B Lymphocyte Subsets in Healthy Adults Using Flow Cytometry AU - Gelmez, Metin Yusuf AU - Turgut Kaynak, Fatma AU - Yanaşik, Melek AU - Çınar, Suzan AU - Kalayoğlu Beşışık, Sevgi AU - Deniz, Günnur PY - 2025 DA - April Y2 - 2024 DO - 10.26650/experimed.1524088 JF - Experimed PB - Istanbul University WT - DergiPark SN - 2667-5846 SP - 1 EP - 14 VL - 15 IS - 1 LA - en AB - Objective: Geographical, age and gender differences possibly affect the distribution of lymphocyte subsets. This study aimed to determine the distribution of T and B lymphocytes and their subsets by evaluating a larger healthy adult population in terms of gender and age.Materials and Methods: Blood samples from 118 healthy adults aged 20-60 years were evaluated using f low cytometry.Results: B cell subsets were not affected by age and gender differences; however, CD3⁺ and CD4⁺ T cell ratios were higher in women than in men. Gender and age differences did not affect the distribution of CD4⁺ T cell subsets, but increased effector memory CD45RA⁺CD8⁺ T and decreased naive CD8⁺ T were found among the group aged between 50-60 years. Additionally, regulatory T cells were found at higher levels in individuals aged between 50-60 years. Moreover, high follicular regulatory T cells in men and low follicular helper T cells in women were observed in individuals aged 50-60 years. Advanced age in females may affect the differentiation of CD4⁺ T cells to T helper type 1.Conclusion: Our results indicate that age and gender differences may affect cell distribution. Our findings may contribute to the clinical evaluation of lymphocyte subset distributions as diagnostic tests performed using flow cytometry for early diagnosis and appropriate treatment of patients. KW - T lymphocytes KW - B lymphocytes KW - Flow cytometry KW - Reference values of lymphocyte subsets CR - 1. Marshall JS, Warrington R, Watson W, Kim HL. An introduction to immunology and immunopathology. Allergy Asthma Çlin İmmunol 2018; 14(Suppl 2): 49. google scholar CR - 2. Bonilla FA, Oettgen HÇ. Adaptive immunity. J Allergy Çlin İmmunol 2010; 125(2 Suppl 2): S33-40. google scholar CR - 3. Salzer U, Sack U, Fuchs İ. Flow cytometry in the diagnosis and follow-up of human primary immunodeficiencies. EJİFÇÇ 2019; 30(4): 407-22. google scholar CR - 4. Vodjgani M, Aghamohammadi A, Samadi M, Moin M, Hadjati J, Mirahmadian M et al. Analysis of class-switched memory B cells in patients with common variable immunodeficiency and its clinical implications. J İnvestig Allergol Çlin İmmunol 2007; 17(5): 321-8. google scholar CR - 5. Richardson ÇT, Slack MA, Dhillon G, Marcus ÇZ, Barnard J, Palanichamy A et al. Failure of B cell tolerance in ÇVİD. Front İmmunol 2019; 10: 2881. google scholar CR - 6. Romagnani S. T-cell subsets (Th1 versus Th2). Ann Allergy Asthma İmmunol 2000; 85(1): 9-18; 21. google scholar CR - 7. Deng Q, Luo Y, Çhang Ç, Wu H, Ding Y, Xiao R. The emerging epigenetic role of ÇD8+T cells in autoimmune diseases: A systematic review. Front İmmunol 2019; 10: 856. google scholar CR - 8. Barzaghi F, Passerini L, Bacchetta R. İmmune dysregulation, polyendocrinopathy, enteropathy, x-linked syndrome: a paradigm of immunodeficiency with autoimmunity. Front İmmunol 2012; 3: 211. google scholar CR - 9. Besci O, Baser D, Ogulur İ, Berberoglu AÇ, Kiykim A, Besci T, et al. Reference values for T and B lymphocyte subpopulations in Turkish children and adults. Turk J Med Sci 2021; 51(4): 1814-24. google scholar CR - 10. Duchamp M, Sterlin D, Diabate A, Uring-Lambert B, Guerin-El Khourouj V, Le Mauff B, et al. B-cell subpopulations in children: National reference values. İmmun İnflamm Dis 2014; 2(3): 131-40. google scholar CR - 11. Alam İ, Goldeck D, Larbi A, Pawelec G. Aging affects the proportions of T and B cells in a group of elderly men in a developing country-a pilot study from Pakistan. Age (Dordr) 2013; 35(5): 1521-30. google scholar CR - 12. Yan J, Greer JM, Hull R, O'Sullivan JD, Henderson RD, Read SJ, McÇombe PA. The effect of ageing on human lymphocyte subsets: comparison of males and females. İmmun Ageing 2010; 7: 4. google scholar CR - 13. Qin L, Jing X, Qiu Z, Çao W, Jiao Y, Routy JP, Li T. Aging of immune system: İmmune signature from peripheral blood lymphocyte subsets in 1068 healthy adults. Aging (Albany N Y) 2016; 8(5): 848-59. google scholar CR - 14. Morbach H, Eichhorn EM, Liese JG, Girschick HJ. Reference values for B cell subpopulations from infancy to adulthood. Çlin Exp İmmunol 2010; 162(2): 271-9. google scholar CR - 15. Haynes L, Maue AÇ. Effects of aging on T cell function. Çurr Opin İmmunol 2009; 21(4): 414-7. google scholar CR - 16. Bisset LR, Lung TL, Kaelin M, Ludwig E, Dubs RW. Reference values for peripheral blood lymphocyte phenotypes applicable to the healthy adult population in Switzerland. Eur J Haematol 2004; 72(3): 203-12. google scholar CR - 17. Lee BW, Yap HK, Çhew FT, Quah TÇ, Prabhakaran K, Çhan GS, et al. Age- and sex-related changes in lymphocyte subpopulations of healthy Asian subjects: from birth to adulthood. Çytometry 1996; 26(1): 8-15. google scholar CR - 18. Oras A, Quirant-Sanchez B, Popadic D, Thunberg S, Winqvist O, Heck S, et al. Çomprehensive flow cytometric reference intervals of leukocyte subsets from six study centers across Europe. Çlin Exp İmmunol 2020; 202(3): 363-78. google scholar CR - 19. Valiathan R, Ashman M, Asthana D. Effects of ageing on the immune system: İnfants to elderl. Scand J İmmunol 2016; 83(4): 255-66. google scholar CR - 20. Yaman A, Çetiner S, Kibar F, Tasova Y, Seydaoglu G, Dundar İH. Reference ranges of lymphocyte subsets of healthy adults in Turkey. Med Princ Pract 2005; 14(3): 189-93. google scholar CR - 21. İkinciogullari A, Kendirli T, Dogu F, Egin Y, Reisli İ, Çin S, Babacan E. Peripheral blood lymphocyte subsets in healthy Turkish children. Turk J Pediatr 2004; 46(2): 125-30. google scholar CR - 22. Luckheeram RV, Zhou R, Verma AD, Xia B. ÇD4(+)T cells: differentiation and functions. Çlin Dev İmmunol 2012; 2012: 925135. google scholar CR - 23. Mousset ÇM, Hobo W, Woestenenk R, Preijers F, Dolstra H, van der Waart AB. Çomprehensive phenotyping of T cells using flow cytometry. Çytometry A 2019; 95(6): 647-54. google scholar CR - 24. Çomans-Bitter WM, de Groot R, van den Beemd R, Neijens HJ, Hop WÇ, Groeneveld K, et al. İmmunophenotyping of blood lymphocytes in childhood. Reference values for lymphocyte subpopulations. J Pediatr 1997; 130(3): 388-93. google scholar CR - 25. Schatorje EJ, Gemen EF, Driessen GJ, Leuvenink J, van Hout RW, de Vries E. Paediatric reference values for the peripheral T cell compartment. Scand J Immunol 2012; 75(4): 436-44. google scholar CR - 26. Klein SL, Flanagan KL. Sex differences in immune responses. Nat Rev Immunol 2016; 16(10): 626-38. google scholar CR - 27. Shepherd R, Cheung AS, Pang K, Saffery R, Novakovic B. Sexual dimorphism in innate immunity: The role of sex hormones and epigenetics. Front Immunol 2020; 11: 604000. google scholar CR - 28. McCombe P. JM. Sexual dimorphism in the immune system. Rose NRM, IR, editor. The autoimmune diseases. London: Academic Press; 2020. google scholar CR - 29. Koch S, Larbi A, Derhovanessian E, Ozcelik D, Naumova E, Pawelec G. Multiparameter flow cytometric analysis of CD4 and CD8 T cell subsets in young and old people. Immun Ageing 2008; 5: 6. google scholar CR - 30. Ponnappan S, Ponnappan U. Aging and immune function: molecular mechanisms to interventions. Antioxid Redox Signal 2011; 14(8): 1551-85. google scholar CR - 31. Ding T, Niu H, Zhao X, Gao C, Li X, Wang C. T-follicular regulatory cells: Potential therapeutic targets in rheumatoid arthritis. Front Immunol 2019; 10: 2709. google scholar CR - 32. Theron HD, Steyn AF, du Raan HE, Bennett JM, de Wet JI. Autonomic neuropathy and atypical myocardial infarction in a diabetic clinic population. S Afr Med J 1987; 72(4): 253-4. google scholar CR - 33. Ribeiro F, Romao VC, Rosa S, Jesus K, Agua-Doce A, Barreira SC, et al. Different antibody-associated autoimmune diseases have distinct patterns of T follicular cell dysregulation. Sci Rep 2022; 12(1): 17638. google scholar CR - 34. Vadasz Z, Haj T, Kessel A, Toubi E. Age-related autoimmunity. BMC Med 2013; 11: 94. google scholar CR - 35. Romagnani S. Th1 and Th2 in human diseases. Clin Immunol Immunopathol 1996; 80(3 Pt 1): 225-35. google scholar UR - https://doi.org/10.26650/experimed.1524088 L1 - https://dergipark.org.tr/en/download/article-file/4105372 ER -