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

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 mod...

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Bibliographic Details
Published in:Kidney international 2009-10, Vol.76 (7), p.717-729
Main Authors: Gandolfo, Maria Teresa, Jang, Hye Ryoun, Bagnasco, Serena M., Ko, Gang-Jee, Agreda, Patricia, Satpute, Shailesh R., Crow, Michael T., King, Landon S., Rabb, Hamid
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Cardiology. Vascular system
Cell Movement - immunology
Cytokines - biosynthesis
Cytokines - immunology
Forkhead Transcription Factors
ischemia-reperfusion
Kidneys
lymphocytes
Medical sciences
Mice
Nephrology. Urinary tract diseases
Regeneration - physiology
renal protection
Reperfusion Injury - immunology
T-Lymphocytes - immunology
T-Lymphocytes, Regulatory - immunology
Time Factors
Urinary system involvement in other diseases. Miscellaneous
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Summary: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.
ISSN:0085-2538
1523-1755
DOI:10.1038/ki.2009.259