[HTML][HTML] Foxp3+ regulatory T cells participate in repair of ischemic acute kidney injury

MT Gandolfo, HR Jang, SM Bagnasco, GJ Ko… - Kidney international, 2009 - Elsevier
MT Gandolfo, HR Jang, SM Bagnasco, GJ Ko, P Agreda, SR Satpute, MT Crow, LS King…
Kidney international, 2009Elsevier
T lymphocytes modulate early ischemia-reperfusion injury in the kidney; however, their role
during repair is unknown. We studied the role of TCRβ+ CD4+ CD25+ Foxp3+ regulatory T
cells (Tregs), known to blunt immune responses, in repair after ischemia-reperfusion injury
to the kidney. Using a murine model of ischemic acute kidney injury we found that there was
a significant trafficking of Tregs into the kidneys after 3 and 10 days. Post-ischemic kidneys
had increased numbers of TCRβ+ CD4+ and TCRβ+ CD8+ T cells with enhanced pro …
T lymphocytes modulate early ischemia-reperfusion injury in the kidney; however, their role during repair is unknown. We studied the role of TCRβ+CD4+CD25+Foxp3+ regulatory T cells (Tregs), known to blunt immune responses, in repair after ischemia-reperfusion injury to the kidney. Using a murine model of ischemic acute kidney injury we found that there was a significant trafficking of Tregs into the kidneys after 3 and 10 days. Post-ischemic kidneys had increased numbers of TCRβ+CD4+ and TCRβ+CD8+ T cells with enhanced pro-inflammatory cytokine production. Treg depletion starting 1 day after ischemic injury using anti-CD25 antibodies increased renal tubular damage, reduced tubular proliferation at both time points, enhanced infiltrating T lymphocyte cytokine production at 3 days and TNF-α generation by TCRβ+CD4+ T cells at 10 days. In separate mice, infusion of CD4+CD25+ Tregs 1 day after initial injury reduced INF-γ production by TCRβ+CD4+ T cells at 3 days, improved repair and reduced cytokine generation at 10 days. Treg manipulation had minimal effect on neutrophil and macrophage infiltration; Treg depletion worsened mortality and serum creatinine, while Treg infusion had a late beneficial effect on serum creatinine in bilateral ischemia. Our study demonstrates that Tregs infiltrate ischemic-reperfused kidneys during the healing process promoting repair, likely through modulation of pro-inflammatory cytokine production of other T cell subsets. Treg targeting could be a novel therapeutic approach to enhance recovery from ischemic acute kidney injury.
Elsevier