Exploring Sex Differences In Immune Cell Profiles Of Male, Premenopausal Female, And Postmenopausal Female Mice To Understand Susceptibility To Immune Mediated Hypertension

T cells are required for the development of hypertension in male and postmenopausal female mice while premenopausal females are protected from T cell mediated hypertension. To better understand sex differences in immune-cell mediated hypertensive responses, we sought to determine if there were any significant differences in the immune cell profiles of premenopausal female (F), VCD-treated postmenopausal female (PMF), and male (M) mice. Spleens were collected from all mice and processed for flow cytometric analysis of T cell populations (n=8/group). Analysis of splenic T cell populations revealed no significant difference in the frequency of CD3+ or CD4+ T cells between groups (CD3+: F 33.4%, PMF 30.3%, M 30.2% of total lymphocytes, CD4+: F 64.8%, PMF 70.7%, M 67.5% of CD3+ cells). However, postmenopausal females had a significantly lower frequency of splenic CD8+ T cells compared to both males and premenopausal females (CD8+: F 27.9%, PMF 19.5%*, M 25.3% of CD3+ cells *p<0.05 vs M and F). Additionally, premenopausal females displayed significantly increased expression of the memory marker CD44 and the anti-inflammatory marker CTLA-4 on CD4+ cells compared to both males and postmenopausal females (MFI CD44: F 334.8*, PMF 269.4, M 280.4, MFI CTLA-4: F 100.7*, PMF 80.9, M 86.8 *p<0.01 vs M and PMF). Additional flow cytometric staining was performed to evaluate sex differences in splenic Antigen Presenting Cell (APC) populations (n=8/group). The frequency of CD11b+ APCs, thought to primarily represent macrophage populations, were significantly reduced in postmenopausal females compared to premenopausal females but there was no significant difference from males (CD11b +: F 14.6%, PMF 11.8%*, M 12.9% of monocytes *p<0.05 vs F). Additionally, CD11c+ dendritic cell populations were found to be significantly reduced in postmenopausal females compared to both males and premenopausal females (CD11c+: F 4.1%, PMF 2.8%*, M 3.9% of all monocytes *p<0.01 vs M and F). Taken together, these results indicate a significant difference in the baseline immune environment between male, premenopausal female and postmenopausal females which likely contribute to sex-differences in susceptibility to immune-mediated hypertension.