LAUSR

September 29, 2020 e189 Daxin Wang, MD Tian Chen , MD Xinquan Yang, MD To the Editor: We read with interest the article titled “White Blood Cells and Blood Pressure: A Mendelian Randomization Study,”1 demonstrating a concordant, positive, and potentially causal relationship of elevated lymphocyte count with higher blood pressure. The adaptive immune response appears to play a key role in blood pressure elevation and end-organ damage. Pollow et al2 found that deficiency of Rag1 in female mice lacking B and T lymphocytes limited the prohypertensive effects of T lymphocytes from males in angiotensin II–induced hypertension, and this protection might involve sex differences in central or renal T lymphocyte infiltration. It should be noted that although they did not detect greater T cell infiltration in male and female mice after angiotensin II infusion, angiotensin II treatment could increase the number of activated T cells and was associated with significantly increased vascular and renal infiltration of CD4+ and CD8+ T cells in male experimental animals.3 Tipton and Sullivan3 also found that removing sex hormones by gonadectomy resulted in significant increases in helper T 17 cells and significant decreases in T regulatory lymphocytes in both male and female subjects, suggesting that sex hormones cannot account for all of these observed sex differences in the T cell profile in spontaneously hypertensive rats. Interestingly, under baseline conditions, male spontaneously hypertensive rats had significantly more helper T 17 cells in their kidneys than female rats, whereas which had more T regulatory lymphocytes.4 Sex differences in T cells are also observed in humans, with the proportion of circulating CD4+ T cells producing more interferon γ being greater in women than in men. CD4+ T cells from men produce more interleukin 17, highlighting the sex differences in T cell subpopulations.4 Because these T lymphocyte subsets and cytokines potentially have opposing effects on blood pressure regulation and polarized T cells possess considerable plasticity to change their phenotype and cytokine secretion depending on the environment where the cells live,5 we speculate that in females, the increase in blood pressure is more dependent on a defect in the ability to suppress proinflammatory T cell infiltration into target organs or functional abnormalities of T regulatory lymphocytes, and we wonder whether the sex of the subject being studied could be considered in the authors’ extended work for providing a novel relationship between sex, immune cells, tissue infiltration, and blood pressure. Future lying in the identification of subsets of different cellular types with different host hormonal milieus or sex chromosome complements may be critical to understanding the role of immune cells in blood pressure control, which allows the development of immune-based therapies in both sexes.