Abstract
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 CD247 gene mutation on the Dahl SS background (SS(CD247-/-)) 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(CD247-/-) 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(CD247-/-) recipients to determine the potential contribution of T cell sex. RESULTS: The lack of functional T cells in SS(CD247-/-) rats significantly reduced salt-induced hypertension and proteinuria in both sexes, although SS(CD247-/-) females exhibited greater protection from kidney damage. Adoptive transfer of either Dahl SS male or female splenocytes into SS(CD247-/-) male recipients exacerbated hypertension and proteinuria compared with controls, while in SS(CD247-/-) 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(CD247-/-) 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.