Sex-Dependency of T Cell-Induced Salt-Sensitive Hypertension and Kidney Damage

Background: It is established that the immune system, namely T cells, plays a role in the development of hypertension and renal damage in male Dahl salt-sensitive (SS) rats, but far less is known about this relationship in females. Rats with genetically deleted T cells via gene mutation on the Dahl SS background (SS) were utilized to interrogate the effect of sex and T cells on salt sensitivity.

Methods: We assessed the hypertensive and kidney injury phenotypes in male versus female SS and SS rats challenged with 3 weeks of high salt (4.0% NaCl). Differences in T cell activation genes were examined in renal T cells from male and female SS rats, and a sex-specific adoptive transfer was performed by injecting male or female splenocytes into either male or female SS recipients to determine the potential contribution of T cell sex.

Results: The lack of functional T cells in SS rats significantly reduced salt-induced hypertension and proteinuria in both sexes, although SS females exhibited greater protection from kidney damage. Adoptive transfer of either Dahl SS male or female splenocytes into SS male recipients exacerbated hypertension and proteinuria compared with controls, while in SS female recipients, exacerbation of disease occurred only upon transfer of male, but not female, SS splenocytes.

Conclusions: The absence of T cells in the SS normalized sex differences in blood pressure, though sex differences in renal damage persisted. Splenocyte transfer experiments demonstrated that salt sensitivity is amplified if the sex of the T cell or the recipient is male.