Immunity, inflammation and disease · 2026
Dynamic Shifts in Lymphocyte Subsets During the Menopausal Transition and Sexual Dimorphism in Immunosenescence.
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Xuan Ci, He Li, Bohan Zhou, Junming Xu, Qingchao Li, Junting Huang
Аннотация
BACKGROUND: Immunosenescence demonstrates marked sexual dimorphism, yet the dynamic changes in lymphocyte subsets across the female menopausal transition are poorly defined. This study characterized these age- and sex-related immune variations in a large Chinese cohort.
METHODS: In this cross-sectional study, we analyzed 4209 healthy adults using flow cytometry to quantify lymphocyte subsets and PD-1 expression. Females were stratified by age and reproductive stage. Sex comparisons were performed after propensity score age-matching.
RESULTS: Analysis of the female cohort revealed dynamic immune shifts during the menopausal transition, characterized by a "scissor-like" pattern: CD3+CD4+ T cells (%) and the CD4/CD8 ratio peaked at 55-59 years, while CD3+CD8+ T cells (%) declined continuously (all p < 0.001). Notably, CD19+ B cells (%) increased with age in females but decreased in males. After age-matching, pronounced sexual dimorphism was confirmed: females exhibited significantly higher levels of CD3+ T cells, CD3+CD4+ T cells, CD19+ B cells, NK cells, and CD4/CD8 ratio, alongside lower PD-1 expression on CD4+ T cells and NK cells (all p < 0.001). In contrast, PD-1 expression on CD8+ T cells was higher in females (p < 0.001).
CONCLUSION: These findings suggest that the perimenopausal period represents a key phase of immune remodeling in women, and support the integration of sex and reproductive stage into future immunosenescence research and clinical strategies.
METHODS: In this cross-sectional study, we analyzed 4209 healthy adults using flow cytometry to quantify lymphocyte subsets and PD-1 expression. Females were stratified by age and reproductive stage. Sex comparisons were performed after propensity score age-matching.
RESULTS: Analysis of the female cohort revealed dynamic immune shifts during the menopausal transition, characterized by a "scissor-like" pattern: CD3+CD4+ T cells (%) and the CD4/CD8 ratio peaked at 55-59 years, while CD3+CD8+ T cells (%) declined continuously (all p < 0.001). Notably, CD19+ B cells (%) increased with age in females but decreased in males. After age-matching, pronounced sexual dimorphism was confirmed: females exhibited significantly higher levels of CD3+ T cells, CD3+CD4+ T cells, CD19+ B cells, NK cells, and CD4/CD8 ratio, alongside lower PD-1 expression on CD4+ T cells and NK cells (all p < 0.001). In contrast, PD-1 expression on CD8+ T cells was higher in females (p < 0.001).
CONCLUSION: These findings suggest that the perimenopausal period represents a key phase of immune remodeling in women, and support the integration of sex and reproductive stage into future immunosenescence research and clinical strategies.