The perimenopausal period represents a key phase of immune remodeling in women, characterized by a 'scissor-like' pattern in T cell subsets and pronounced sexual dimorphism in lymphocyte composition and PD-1 expression.
CD3+CD4+ T cells (%) and the CD4/CD8 ratio peaked at ages 55-59 years in females, while CD3+CD8+ T cells (%) declined continuously across age groups.
CD19+ B cells (%) showed opposite age-related trajectories by sex: increasing with age in females but decreasing in males.
After age-matching, females exhibited significantly higher levels of CD3+ T cells, CD3+CD4+ T cells, CD19+ B cells, NK cells, and CD4/CD8 ratio compared to males.
Females showed lower PD-1 expression on CD4+ T cells and NK cells compared to males, but higher PD-1 expression on CD8+ T cells.
The study characterized age- and sex-related immune variations using flow cytometry in a large cross-sectional cohort of 4209 healthy Chinese adults.
The menopausal transition was identified as a key phase of immune remodeling in women, supporting the integration of sex and reproductive stage into immunosenescence research.
This research suggests that a woman's immune system undergoes significant reorganization during the transition through menopause, and that men and women age immunologically in distinctly different ways. Studying over 4,000 healthy Chinese adults, researchers tracked key immune cell types across age groups and found a striking 'scissor-like' pattern in women: one type of infection-fighting T cell (CD4+) and the ratio of CD4 to CD8 T cells peaked in women aged 55–59, while another type (CD8+) steadily declined throughout life. Meanwhile, B cells—important for antibody production—increased with age in women but decreased in men, illustrating how the same aging process can affect the immune system very differently depending on sex. When the researchers carefully compared men and women of the same age, women consistently had higher levels of several immune cell types, including T cells, B cells, and NK cells, as well as lower levels of a protein called PD-1 on certain immune cells. PD-1 is associated with immune cell exhaustion or reduced activity; lower levels generally suggest more active immune responses. However, women had higher PD-1 on a different subset of immune cells (CD8+ T cells), indicating the relationship between sex and immune function is complex and cell-type specific. This research suggests that using a person's chronological age alone is insufficient to understand their immune health, particularly for women. The menopausal transition appears to be a pivotal window of immune change, and future medical research and clinical approaches—such as vaccine strategies or assessments of immune-related disease risk—may benefit from taking both biological sex and reproductive stage into account.
Xuan C, He L, Bohan Z, Junming X, Qingchao L, Junting H. (2026). Dynamic Shifts in Lymphocyte Subsets During the Menopausal Transition and Sexual Dimorphism in Immunosenescence.. Immunity, inflammation and disease. https://doi.org/10.1002/iid3.70558