Decoupled dynamics of absolute and relative lymphocyte counts and age−polarized CD4+/CD8+ ratio in infants versus older adults

BackgroundSignificant phenotypic and functional differences in peripheral lymphocyte subsets between infants and the elderly contribute to age-related variations in disease susceptibility and clinical outcomes. However, we are unable to specifically analyze the underlying causes owing to a lack of d...

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Main Authors: Ting Ge, Guixin He, Qian Cui, Shuangcui Wang, Zekun Wang, Yingying Xie, Yuanyuan Tian, Juyue Zhou, Wentao Li, Baohui Wang, Keming Zhang, Jianchun Yu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1599515/full
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author Ting Ge
Ting Ge
Ting Ge
Guixin He
Guixin He
Guixin He
Qian Cui
Qian Cui
Qian Cui
Shuangcui Wang
Shuangcui Wang
Shuangcui Wang
Zekun Wang
Yingying Xie
Yingying Xie
Yingying Xie
Yuanyuan Tian
Yuanyuan Tian
Yuanyuan Tian
Juyue Zhou
Juyue Zhou
Juyue Zhou
Wentao Li
Wentao Li
Baohui Wang
Keming Zhang
Jianchun Yu
Jianchun Yu
author_facet Ting Ge
Ting Ge
Ting Ge
Guixin He
Guixin He
Guixin He
Qian Cui
Qian Cui
Qian Cui
Shuangcui Wang
Shuangcui Wang
Shuangcui Wang
Zekun Wang
Yingying Xie
Yingying Xie
Yingying Xie
Yuanyuan Tian
Yuanyuan Tian
Yuanyuan Tian
Juyue Zhou
Juyue Zhou
Juyue Zhou
Wentao Li
Wentao Li
Baohui Wang
Keming Zhang
Jianchun Yu
Jianchun Yu
author_sort Ting Ge
collection DOAJ
description BackgroundSignificant phenotypic and functional differences in peripheral lymphocyte subsets between infants and the elderly contribute to age-related variations in disease susceptibility and clinical outcomes. However, we are unable to specifically analyze the underlying causes owing to a lack of data on lymphocyte absolute counts and functional markers from two extremes of age.MethodsA total of 111 infants (≤ 6 months) and 111 older adults (≥ 65 years) were enrolled to assess the percentages and absolute counts of peripheral blood lymphocyte (PBL) subsets. These included CD3+ T cells, CD4+ T cells, CD8+ T cells, B cells, NK cells, naïve T cells (Tn), stem cell memory T cells (Tscm), central memory T cells (Tcm), effector memory T cells (Tem), and terminally differentiated effector memory T cells (Temra). Differences in PBL phenotypes by age group and gender were analyzed using the Wilcoxon rank-sum test. In addition, linear regression analysis was performed to examine the associations between the CD4+/CD8+ ratio and various PBL subsets.ResultsComparative analysis demonstrated that infants had significantly higher absolute counts of CD3+ T cells, CD4+ T cells, CD8+ T cells, B cells, and both CD4+ and CD8+ subsets of Tn, Tscm, Tcm, and Temra (p < 0.001), despite significantly lower percentages of these cell types (p < 0.001). In contrast, older adults exhibited reduced absolute counts but relevated percentages for all the aforementioned lymphocyte subsets, except for CD4+ and CD8+ Tn cells, which showed lower percentages (p < 0.001). Notably, NK cells were significantly increased in both percentage and absolute count among older adults (p < 0.001). The CD4+/CD8+ ratio showed marked age-related polarization, with significantly higher values in infants compared to older adults (median, 2.60 [IQR, 2.02–3.36] vs. 1.60 [IQR, 1.15–2.14]), a difference particularly pronounced in female infants (p < 0.001). Gender-related differences were observed only in the infant group, where female infants exhibited significantly higher absolute counts of CD3+ T cells, CD3+CD4+ T cells, and CD4+ Tscm and Tcm subsets (p < 0.05). Furthermore, linear regression analysis revealed that in infants, the CD4+/CD8+ ratio was positively associated with the percentages and absolute counts of CD4+ Tn cells and the percentage of CD4+ Tcm cells (p < 0.05), while showing a negative correlation with the percentages of CD8+ Tn and memory T (Tm) cell subsets (p < 0.05).ConclusionPBL profiles exhibit marked heterogeneity at the extremes of age, with infants showing abundant naïve and memory T cell reserves, while older adults are characterized by increased NK cell activity. The age-dependent polarization of the CD4+/CD8+ ratio may serve as a potential biomarker of immunosenescence, offering valuable reference points for age-tailored vaccination strategies and immune risk stratification in the elderly.
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spelling doaj-art-d56ed7c7d0ca4ef8af155d2676be36502025-08-20T03:13:49ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.15995151599515Decoupled dynamics of absolute and relative lymphocyte counts and age−polarized CD4+/CD8+ ratio in infants versus older adultsTing Ge0Ting Ge1Ting Ge2Guixin He3Guixin He4Guixin He5Qian Cui6Qian Cui7Qian Cui8Shuangcui Wang9Shuangcui Wang10Shuangcui Wang11Zekun Wang12Yingying Xie13Yingying Xie14Yingying Xie15Yuanyuan Tian16Yuanyuan Tian17Yuanyuan Tian18Juyue Zhou19Juyue Zhou20Juyue Zhou21Wentao Li22Wentao Li23Baohui Wang24Keming Zhang25Jianchun Yu26Jianchun Yu27Central Laboratory, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaGraduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaNational Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaCentral Laboratory, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaGraduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaNational Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaCentral Laboratory, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaGraduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaNational Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaCentral Laboratory, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaGraduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaNational Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaDepartment of Biostatistics, School of Global Public Health, New York University, New York, NY, United StatesCentral Laboratory, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaGraduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaNational Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaCentral Laboratory, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaGraduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaNational Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaCentral Laboratory, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaGraduate School, Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaNational Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaNational Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaDepartment of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaThe First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Chinese Medical University, Hangzhou, ChinaDepartment of Nutrition, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaCentral Laboratory, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaNational Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, ChinaBackgroundSignificant phenotypic and functional differences in peripheral lymphocyte subsets between infants and the elderly contribute to age-related variations in disease susceptibility and clinical outcomes. However, we are unable to specifically analyze the underlying causes owing to a lack of data on lymphocyte absolute counts and functional markers from two extremes of age.MethodsA total of 111 infants (≤ 6 months) and 111 older adults (≥ 65 years) were enrolled to assess the percentages and absolute counts of peripheral blood lymphocyte (PBL) subsets. These included CD3+ T cells, CD4+ T cells, CD8+ T cells, B cells, NK cells, naïve T cells (Tn), stem cell memory T cells (Tscm), central memory T cells (Tcm), effector memory T cells (Tem), and terminally differentiated effector memory T cells (Temra). Differences in PBL phenotypes by age group and gender were analyzed using the Wilcoxon rank-sum test. In addition, linear regression analysis was performed to examine the associations between the CD4+/CD8+ ratio and various PBL subsets.ResultsComparative analysis demonstrated that infants had significantly higher absolute counts of CD3+ T cells, CD4+ T cells, CD8+ T cells, B cells, and both CD4+ and CD8+ subsets of Tn, Tscm, Tcm, and Temra (p < 0.001), despite significantly lower percentages of these cell types (p < 0.001). In contrast, older adults exhibited reduced absolute counts but relevated percentages for all the aforementioned lymphocyte subsets, except for CD4+ and CD8+ Tn cells, which showed lower percentages (p < 0.001). Notably, NK cells were significantly increased in both percentage and absolute count among older adults (p < 0.001). The CD4+/CD8+ ratio showed marked age-related polarization, with significantly higher values in infants compared to older adults (median, 2.60 [IQR, 2.02–3.36] vs. 1.60 [IQR, 1.15–2.14]), a difference particularly pronounced in female infants (p < 0.001). Gender-related differences were observed only in the infant group, where female infants exhibited significantly higher absolute counts of CD3+ T cells, CD3+CD4+ T cells, and CD4+ Tscm and Tcm subsets (p < 0.05). Furthermore, linear regression analysis revealed that in infants, the CD4+/CD8+ ratio was positively associated with the percentages and absolute counts of CD4+ Tn cells and the percentage of CD4+ Tcm cells (p < 0.05), while showing a negative correlation with the percentages of CD8+ Tn and memory T (Tm) cell subsets (p < 0.05).ConclusionPBL profiles exhibit marked heterogeneity at the extremes of age, with infants showing abundant naïve and memory T cell reserves, while older adults are characterized by increased NK cell activity. The age-dependent polarization of the CD4+/CD8+ ratio may serve as a potential biomarker of immunosenescence, offering valuable reference points for age-tailored vaccination strategies and immune risk stratification in the elderly.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1599515/fullperipheral blood lymphocyte subsetsabsolute countsCD4 +/CD8 + ratioinfantsolder adults
spellingShingle Ting Ge
Ting Ge
Ting Ge
Guixin He
Guixin He
Guixin He
Qian Cui
Qian Cui
Qian Cui
Shuangcui Wang
Shuangcui Wang
Shuangcui Wang
Zekun Wang
Yingying Xie
Yingying Xie
Yingying Xie
Yuanyuan Tian
Yuanyuan Tian
Yuanyuan Tian
Juyue Zhou
Juyue Zhou
Juyue Zhou
Wentao Li
Wentao Li
Baohui Wang
Keming Zhang
Jianchun Yu
Jianchun Yu
Decoupled dynamics of absolute and relative lymphocyte counts and age−polarized CD4+/CD8+ ratio in infants versus older adults
Frontiers in Immunology
peripheral blood lymphocyte subsets
absolute counts
CD4 +/CD8 + ratio
infants
older adults
title Decoupled dynamics of absolute and relative lymphocyte counts and age−polarized CD4+/CD8+ ratio in infants versus older adults
title_full Decoupled dynamics of absolute and relative lymphocyte counts and age−polarized CD4+/CD8+ ratio in infants versus older adults
title_fullStr Decoupled dynamics of absolute and relative lymphocyte counts and age−polarized CD4+/CD8+ ratio in infants versus older adults
title_full_unstemmed Decoupled dynamics of absolute and relative lymphocyte counts and age−polarized CD4+/CD8+ ratio in infants versus older adults
title_short Decoupled dynamics of absolute and relative lymphocyte counts and age−polarized CD4+/CD8+ ratio in infants versus older adults
title_sort decoupled dynamics of absolute and relative lymphocyte counts and age polarized cd4 cd8 ratio in infants versus older adults
topic peripheral blood lymphocyte subsets
absolute counts
CD4 +/CD8 + ratio
infants
older adults
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1599515/full
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