Female spontaneously hypertensive rats have greater renal anti-inflammatory T lymphocyte infiltration than males

Ashlee J. Tipton, Babak Baban, Jennifer C Sullivan

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

T cells contribute to hypertension in male experimental models; data in females is lacking even though women are more likely to develop immune disorders. The goal of this study was to determine whether immune cells contribute to hypertension in female spontaneously hypertensive rats (SHR) and define the T cell profile in whole blood and kidneys of male and female SHR. We hypothesized that inflammatory cells contribute to hypertension in female SHR; however, male SHR have a higher blood pressure so we hypothesize they will have a heightened inflammatory profile. The lymphocyte inhibitor mycophenolate mofetil (MMF) was administered in a dose-dependent manner to SHR. At the highest dose (50 mg·kg -1·day -1), blood pressure was significantly decreased in both sexes, yet the percent decrease in blood pressure was greater in females (female: 12 ± 1%; males: 7 ± 1%, P = 0.01). Circulating and renal T cell profiles were defined using analytical flow cytometry. Female SHR had more circulating CD3 +, CD4 +, and pro-inflammatory CD3 +CD4 +RORγ+ Th17 cells, whereas males had more immune-suppressive CD3 +CD4 +Foxp3 + T regulatory cells. In the kidney, females had greater numbers of CD8 + and T regulatory cells than males, whereas males had greater CD4 + and Th17 cell infiltration. MMF decreased circulating and renal T cells in both sexes (P < 0.0001), although the effect of MMF on T cell subtypes was sex specific with females having greater sensitivity to MMF-induced decreases in lymphocytes. In conclusion, there is a lymphocyte contribution to the maintenance of hypertension in the female SHR and sex of the animal impacts the T cell profile.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume303
Issue number4
DOIs
StatePublished - Aug 15 2012

Fingerprint

Inbred SHR Rats
Anti-Inflammatory Agents
T-Lymphocytes
Kidney
Mycophenolic Acid
Hypertension
Th17 Cells
Regulatory T-Lymphocytes
Lymphocytes
Thomsen-Friedenreich antibodies
Blood Pressure
Immune System Diseases
Flow Cytometry
Theoretical Models
Maintenance

Keywords

  • Blood pressure
  • Gender
  • Mycophenylate mofetil
  • T cells

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

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title = "Female spontaneously hypertensive rats have greater renal anti-inflammatory T lymphocyte infiltration than males",
abstract = "T cells contribute to hypertension in male experimental models; data in females is lacking even though women are more likely to develop immune disorders. The goal of this study was to determine whether immune cells contribute to hypertension in female spontaneously hypertensive rats (SHR) and define the T cell profile in whole blood and kidneys of male and female SHR. We hypothesized that inflammatory cells contribute to hypertension in female SHR; however, male SHR have a higher blood pressure so we hypothesize they will have a heightened inflammatory profile. The lymphocyte inhibitor mycophenolate mofetil (MMF) was administered in a dose-dependent manner to SHR. At the highest dose (50 mg·kg -1·day -1), blood pressure was significantly decreased in both sexes, yet the percent decrease in blood pressure was greater in females (female: 12 ± 1{\%}; males: 7 ± 1{\%}, P = 0.01). Circulating and renal T cell profiles were defined using analytical flow cytometry. Female SHR had more circulating CD3 +, CD4 +, and pro-inflammatory CD3 +CD4 +RORγ+ Th17 cells, whereas males had more immune-suppressive CD3 +CD4 +Foxp3 + T regulatory cells. In the kidney, females had greater numbers of CD8 + and T regulatory cells than males, whereas males had greater CD4 + and Th17 cell infiltration. MMF decreased circulating and renal T cells in both sexes (P < 0.0001), although the effect of MMF on T cell subtypes was sex specific with females having greater sensitivity to MMF-induced decreases in lymphocytes. In conclusion, there is a lymphocyte contribution to the maintenance of hypertension in the female SHR and sex of the animal impacts the T cell profile.",
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