HLA-DR+ CD45RA- Tregs and CD28- Treg-like cells: Potential immunologic biomarkers for reproductive aging

Abstract

Problem: This study aimed to identify subsets of regulatory T cells (Tregs) associated with ovarian aging and determine whether they can be used as markers of reproductive aging.

Method: This prospective cohort study was conducted among women of reproductive age. Basic physiological characteristics, reproductive hormones, Treg cell subsets, and correlations between these parameters were assessed. The POSEIDON criteria was used to identify women with low reproductive potential.

Results: The percentages of HLA-DR⁺ CD45RA- Tregs and CD28- Treg-like cells significantly increased with age. Women between 40 and 49 years had significantly higher percentages of HLA-DR⁺ CD45RA- Tregs and CD28- Treg-like cells than those at 20-29, 30-34, and 35-39 years old. Age positively correlated with FSH levels and the percentages of HLA-DR⁺ CD45RA- Tregs and CD28- Treg-like cells, but inversely correlated with antral follicle count (AFC) and AMH levels. Interestingly, a positive correlation was found between the percentages of HLA-DR⁺ CD45RA- Tregs and FSH levels, whereas an inverse correlation was found between those of HLA-DR⁺ CD45RA- Tregs and AFC or AMH levels. Furthermore, a significant positive correlation was observed between the percentages of CD28- Treg-like cells and AFC. Based on POSEIDON criteria, women with the percentages of HLA-DR⁺ CD45RA- Tregs and CD28- Treg-like cells above reference value ranges were assigned to the low prognosis groups.

Conclusion: These findings suggest that HLA-DR⁺ CD45RA- Tregs and CD28- Treg-like cells can be used as immunologic markers of reproductive aging, which helps clinicians identify women with low reproductive potential and establish individualized therapeutic strategies.

Keywords: CD28ˉ Treg-like cell; HLA-DR⁺CD45RAˉ Treg cell; aging; immunologic markers; reproductive potential.