Time Course of Immune Cell Infiltration and Cytokine Production in the Kidneys of Dahl Salt‐Sensitive (SS) Rats

Abstract

Inflammation and immunity has been implicated in hypertension and renal disease in animals and humans. Previous studies from our lab have demonstrated that pharmacological or genetic inhibition of immune cell infiltration in the kidney attenuates salt‐sensitive hypertension and kidney damage in SS rats. The present studies were performed to assess the temporal infiltration of different immune cell subsets into the kidneys of Dahl SS rats when maintained on a low salt (0.4% NaCl, Day 0) diet and after 7, 14 and 21 days of high salt (4.0% NaCl) intake. Using a flow cytometry‐based approach, a progressive increase of infiltrating cells in the kidneys of Dahl SS was observed with time on the high NaCl diet. The total number of CD45+ cells (9.3±1.96 vs 35.2±6.8 x 105 cells/kidney), CD3+CD8+ cells (.69±.13 vs 1.9±0.2 x 105 cells/kidney) and CD3+CD4+ cells (.36±.08 vs 1.78±0.37 x 105 cells/kidney) significantly increased from Day 0 to 21 of a high salt diet (n=9‐17 rats/group). Stimulation of isolated kidney cells with PMA and ionomycin followed by intracellular cytokine staining revealed an increase in the number of IFN‐g producing CD8+ T cells and also in TNF, IFN‐g and IL‐17 producing CD4+ T cells (e.g. CD3+CD4+IL‐17+ cells increased from .05±.01 to .56±.16 x 105 cells/kidney from Day 0 to Day 21). IFN‐g and IL‐17 production by CD4+ T cells positively correlated with the number of regulatory T cells (increased from .09±.02 to .43±.01 x 105 cells/kidney from Day 0 to 21) and the total number of activated CD4+ T cells (increased from .14±.02 to .84±.02 x 105 cells/kidney from Day 0 to 21). These data indicate that the time course of immune cells infiltration and cytokine production by T cells parallels hypertension and kidney damage in Dahl SS rats fed a high salt diet.This work is supported by DK‐96859 and HL116264.