Systematic review and quantitative meta-analysis of age-dependent human T-lymphocyte homeostasis

ObjectiveTo evaluate and quantitatively describe age-dependent homeostasis for a broad range of total T-cells and specific T-lymphocyte subpopulations in healthy human subjects.MethodsA systematic literature review was performed to identify and collect relevant quantitative information on T-lymphocy...

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Main Authors: Victoria Kulesh, Kirill Peskov, Gabriel Helmlinger, Gennady Bocharov
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-01-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1475871/full
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author Victoria Kulesh
Victoria Kulesh
Kirill Peskov
Kirill Peskov
Kirill Peskov
Gabriel Helmlinger
Gennady Bocharov
Gennady Bocharov
Gennady Bocharov
author_facet Victoria Kulesh
Victoria Kulesh
Kirill Peskov
Kirill Peskov
Kirill Peskov
Gabriel Helmlinger
Gennady Bocharov
Gennady Bocharov
Gennady Bocharov
author_sort Victoria Kulesh
collection DOAJ
description ObjectiveTo evaluate and quantitatively describe age-dependent homeostasis for a broad range of total T-cells and specific T-lymphocyte subpopulations in healthy human subjects.MethodsA systematic literature review was performed to identify and collect relevant quantitative information on T-lymphocyte counts in human blood and various organs. Both individual subject and grouped (aggregated) data on T-lymphocyte observations in absolute and relative values were digitized and curated; cell phenotypes, gating strategies for flow cytometry analyses, organs from which observations were obtained, subjects’ number and age were also systematically inventoried. Age-dependent homeostasis of each T-lymphocyte subpopulation was evaluated via a weighted average calculation within pre-specified age intervals, using a piece-wise equal-effect meta-analysis methodology.ResultsIn total, 124 studies comprising 11722 unique observations from healthy subjects encompassing 20 different T-lymphocyte subpopulations – total CD45+ and CD3+ lymphocytes, as well as specific CD4+ and CD8+ naïve, recent thymic emigrants, activated, effector and various subpopulations of memory T-lymphocytes (total-memory, central-memory, effector-memory, resident-memory) – were systematically collected and included in the final database for a comprehensive analysis. Blood counts of most T-lymphocyte subpopulations demonstrate a decline with age, with a pronounced decrease within the first 10 years of life. Conversely, memory T-lymphocytes display a tendency to increase in older age groups, particularly after ~50 years of age. Notably, an increase in T-lymphocyte numbers is observed in neonates and infants (0 – 1 year of age) towards less differentiated T-lymphocyte subpopulations, while an increase into more differentiated subpopulations emerges later (1 – 5 years of age).ConclusionA comprehensive systematic review and meta-analysis of T-lymphocyte age-dependent homeostasis in healthy humans was performed, to evaluate immune T-cell profiles as a function of age and to characterize generalized estimates of T-lymphocyte counts across age groups. Our study introduces a quantitative description of the fundamental parameters characterizing the maintenance and evolution of T-cell subsets with age, based on a comprehensive integration of available organ-specific and systems-level flow cytometry datasets. Overall, it provides the most up-to-date view of physiological T-cell dynamics and its variance and may be used as a consistent reference for gaining further mechanistic understanding of the human immune status in health and disease.
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spelling doaj-art-711809323c5b4ea28d444976a837534c2025-01-27T06:40:47ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011610.3389/fimmu.2025.14758711475871Systematic review and quantitative meta-analysis of age-dependent human T-lymphocyte homeostasisVictoria Kulesh0Victoria Kulesh1Kirill Peskov2Kirill Peskov3Kirill Peskov4Gabriel Helmlinger5Gennady Bocharov6Gennady Bocharov7Gennady Bocharov8Research Center of Model-Informed Drug Development, I.M. Sechenov First Moscow State Medical University, Moscow, RussiaMarchuk Institute of Numerical Mathematics of the Russian Academy of Sciences (INM RAS), Moscow, RussiaResearch Center of Model-Informed Drug Development, I.M. Sechenov First Moscow State Medical University, Moscow, RussiaMarchuk Institute of Numerical Mathematics of the Russian Academy of Sciences (INM RAS), Moscow, RussiaModeling & Simulation Decisions FZ-LLC, Dubai, United Arab EmiratesQuantitative Medicines LLC, Boston, MA, United StatesMarchuk Institute of Numerical Mathematics of the Russian Academy of Sciences (INM RAS), Moscow, RussiaInstitute for Computer Science and Mathematical Modelling, I.M. Sechenov First Moscow State Medical University, Moscow, RussiaMoscow Center of Fundamental and Applied Mathematics at INM RAS, Moscow, RussiaObjectiveTo evaluate and quantitatively describe age-dependent homeostasis for a broad range of total T-cells and specific T-lymphocyte subpopulations in healthy human subjects.MethodsA systematic literature review was performed to identify and collect relevant quantitative information on T-lymphocyte counts in human blood and various organs. Both individual subject and grouped (aggregated) data on T-lymphocyte observations in absolute and relative values were digitized and curated; cell phenotypes, gating strategies for flow cytometry analyses, organs from which observations were obtained, subjects’ number and age were also systematically inventoried. Age-dependent homeostasis of each T-lymphocyte subpopulation was evaluated via a weighted average calculation within pre-specified age intervals, using a piece-wise equal-effect meta-analysis methodology.ResultsIn total, 124 studies comprising 11722 unique observations from healthy subjects encompassing 20 different T-lymphocyte subpopulations – total CD45+ and CD3+ lymphocytes, as well as specific CD4+ and CD8+ naïve, recent thymic emigrants, activated, effector and various subpopulations of memory T-lymphocytes (total-memory, central-memory, effector-memory, resident-memory) – were systematically collected and included in the final database for a comprehensive analysis. Blood counts of most T-lymphocyte subpopulations demonstrate a decline with age, with a pronounced decrease within the first 10 years of life. Conversely, memory T-lymphocytes display a tendency to increase in older age groups, particularly after ~50 years of age. Notably, an increase in T-lymphocyte numbers is observed in neonates and infants (0 – 1 year of age) towards less differentiated T-lymphocyte subpopulations, while an increase into more differentiated subpopulations emerges later (1 – 5 years of age).ConclusionA comprehensive systematic review and meta-analysis of T-lymphocyte age-dependent homeostasis in healthy humans was performed, to evaluate immune T-cell profiles as a function of age and to characterize generalized estimates of T-lymphocyte counts across age groups. Our study introduces a quantitative description of the fundamental parameters characterizing the maintenance and evolution of T-cell subsets with age, based on a comprehensive integration of available organ-specific and systems-level flow cytometry datasets. Overall, it provides the most up-to-date view of physiological T-cell dynamics and its variance and may be used as a consistent reference for gaining further mechanistic understanding of the human immune status in health and disease.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1475871/fullimmune agingT-lymphocytessystematic reviewmeta-analysishealthy subjects
spellingShingle Victoria Kulesh
Victoria Kulesh
Kirill Peskov
Kirill Peskov
Kirill Peskov
Gabriel Helmlinger
Gennady Bocharov
Gennady Bocharov
Gennady Bocharov
Systematic review and quantitative meta-analysis of age-dependent human T-lymphocyte homeostasis
Frontiers in Immunology
immune aging
T-lymphocytes
systematic review
meta-analysis
healthy subjects
title Systematic review and quantitative meta-analysis of age-dependent human T-lymphocyte homeostasis
title_full Systematic review and quantitative meta-analysis of age-dependent human T-lymphocyte homeostasis
title_fullStr Systematic review and quantitative meta-analysis of age-dependent human T-lymphocyte homeostasis
title_full_unstemmed Systematic review and quantitative meta-analysis of age-dependent human T-lymphocyte homeostasis
title_short Systematic review and quantitative meta-analysis of age-dependent human T-lymphocyte homeostasis
title_sort systematic review and quantitative meta analysis of age dependent human t lymphocyte homeostasis
topic immune aging
T-lymphocytes
systematic review
meta-analysis
healthy subjects
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1475871/full
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