Sex differences in cytokine induction by activated T cells from hypertensive BPH/2 and normotensive BPN/3 mice

Over the past two decades, considerable evidence has emerged to implicate a role for the immune system in the development of hypertension. Previous studies have shown immune cells contribute to the development of hypertension in multiple animal models, however the role of the immune system in spontaneously hypertensive BPH/2 mice is not clear. In the current studies, found T cells derived from male hypertensive BPH/2 mice demonstrated an attenuated activation as compared to those derived from male BPN/3 normotensive mice. However, we also observed striking sex differences in T cell cytokine production in these strains. At 24 h post activation, in comparison to male BPH/2 mice, activated T cells from male BPN/3 mice secreted more IL-2, IL-3, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-22 and TNF. In contrast to male mice, less than half of these cytokines were different between strains in female mice. We also noted marked differences in early Th17 cytokine production in which IL-17A, IL-17F and IL-22 were greater in the male, but not female, BPN/3 groups. Taken together, the data suggest that polyclonally activated T cells from male, and to a much lesser extent, female BPH/2 mice have a weaker cytokine response as compared to T cells from BPN/3 mice which may be due to an overall attenuated activation of T cells from male BPH/2 mice. Overall, while there are striking differences in T cell response between the BPH2 and BPN/3 strains in male mice, the data indicate far fewer differences between the strains in female mice.