Decoupled Dynamics of Absolute and Relative Lymphocyte Counts and Age-Polarized CD4 + /CD8 + Ratio in Infants versus Older Adults

Jianchun Yu^1*Ting Ge¹Guixin He¹Qian Cui¹Shuangcui Wang¹Zekun Wang²Yingying Xie¹Yuanyuan Tian¹Juyue Zhou¹Wentao Li¹Baohui Wang^3*Keming Zhang^1*

• ¹First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Nankai District, China
• ²School of Global Public Health, New York University, New York, New York, United States
• ³First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China

Background: Significant 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. Methods: A 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. Results: This study revealed age-related immune dynamics in peripheral blood lymphocytes, showing infants had significantly higher absolute counts of CD3+/CD4+/CD8+ T cells, B cells, and Tn/Tscm/Tcm/Temra subsets (p < 0.001) compared to older adults, with lower percentages (p < 0.001). The CD4+/CD8+ratio was significantly higher in infants (median 2.60 [IQR 2.02–3.36]) than older adults (1.60 [1.15–2.14]), particularly in females (p < 0.001). Gender differences were observed only in infants, with females showing higher CD3+ T cell and CD4+ Tscm/Tcm counts (p < 0.05). Linear regression confirmed a positive correlation between the CD4+/CD8+ratio and CD4+ Tn/Tcm percentages/counts, and a negative correlation with CD8+ Tn/Tm subset percentages (p < 0.05). Conclusion: PBL 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.