Sex Differences in Cytokine Response by Activated T Cells Derived from Hypertensive BPH/2 and Normotensive BPN/3 Mice
Abstract Body: Over the past two decades, considerable evidence has emerged to implicate a role for the immune system in the development of hypertension. Previously our lab characterized marked differences in immune cell function between hypertensive BPH/2 mice and normotensive BPN/3 mice with a focus on male mice. In the current studies, we characterized differences in T cell cytokine secretion in both male and female mice in the BPH/2 and BPN/3 strains. Similar to our previous study, T cells derived from male 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. Some of the most notable differences were in cytokines that are robustly induced early after activation. Specifically, in comparison to male BPH/2 mice, activated T cells from male BPN/3 mice secreted more IL-2 (BPN/3: 5301 pg/ml ± 2156 vs. BPH/2: 271.11 ± 34.33), IL-6 (BPN/3: 762.1 ± 152.2 vs. BPH/2: 91.18 ± 24.14) and TNFα (BPN/3: 199.0 ± 49.9 vs. BPH/2: 14.73 ± 2.381). In contrast to the male mice, there were no statistical differences between these two strains in these cytokines in the female mice. We also noted marked differences in Th17 cytokine production in which IL-17A, IL-17F, IL-22 and TNFβ were greater in the male, but not female, BPN/3 groups. Likewise, other cytokines such as IL-3, IL-4 and LIF were greater in T cells derived from male, but not female, BPN/3 mice as compared BPH/2 mice. While most cytokines were different between sexes, some were not. In particular, we found that while IL-5, IL-10, GM-CSF and IFNγ were greater in the BPN/3 groups compared BPH/2 groups, these effects were consistent between males and females. In males, most cytokines were much greater in the BPN/3 groups, however this was not the case for IL-9 which was not different between strains or sexes. Taken together, the data suggest that polyclonally activated T cells from male, but not 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.
Rockwell, Cheryl
( Michigan State University
, East Lansing
, Michigan
, United States
)
Dattmore, Devon
( Michigan State University
, Lansing
, Michigan
, United States
)
Leipprandt, Jeffrey R.
( Michigan State University
, East Lansing
, Michigan
, United States
)
Mckenzie, Mckenzie
( Michigan State University
, East Lansing
, Michigan
, United States
)
Garver, Hannah
( Michigan State University
, East Lansing
, Michigan
, United States
)
Lauver, Adam
( Michigan State University
, East Lansing
, Michigan
, United States
)
Author Disclosures:
Cheryl Rockwell:DO NOT have relevant financial relationships
| DEVON DATTMORE:DO NOT have relevant financial relationships
| Jeffrey R. Leipprandt:No Answer
| McKenzie McKenzie:No Answer
| Hannah Garver:No Answer
| Adam Lauver:DO NOT have relevant financial relationships