(196) Characterizing the role of ovarian hormones in regulating sex differences in baseline immune parameters

Introduction/Rationale: Sex differences among peripheral blood mononuclear cells (PBMCs) have been previously described in humans, including greater percentages (%) of CD4+ T cells in females (XX) and greater % of natural killer cells in males (XY). The role of the ovaries in regulating these and other sex differences is unknown.

Methods: We collected PBMCs from 80 age-matched participants (reported as mean ± SEM) and stratified into control females (n=28; 41.6 ± 1.0 years), control males (n=20; 40.4 ± 1.3 years), bilateral salpingo-oophorectomy (BSO) recipients (n=16; 46.1 ± 2.0 years), and BSO recipients receiving hormone therapy (HT) (n=16; 45.7 ± 1.2). BSO recipients were at least 1 year out from surgery. PBMCs were isolated to analyze subsets by single-cell mass cytometry. Serum was collected for estradiol (E2), testosterone (T), and progesterone measurements, and cytokines were quantified using the O-LINK platform.

Results: Three serum markers (IL-10, IL-17c, and CXCL11) showed a sex difference, with greater levels in males; no cytokine was modulated by BSO. Among CD45+ PBMCs, females had a greater % of CD3+ T cells, whereas the % of monocytes were greater in males. However, the sex difference in monocytes disappeared when accounting for T cell differences. Within CD4+ T cells, males had higher % of regulatory T cells and circulating follicular T cells, while within CD8+ T cells, they had higher percentages of PD-1+ effector and terminally differentiated subsets. No highlighted sex difference was associated with the presence of the ovaries. Further explorations identified a negative correlation of % of CD3+ T cells with T levels. Though not driving the sex differences, BSO did increase the % of naïve B cells at the expense of memory B cells, and this was reversed with HT. The % of naïve B cells negatively correlated with E2 and T levels.

Conclusion: The ovaries are not a major regulator of sex differences in immune subsets but do repress the generation of naïve B cells.