IL-2/Anti-IL-2 Complex Attenuates Renal Ischemia-Reperfusion Injury through Expansion of Regulatory T Cells

• Published in: Journal of the American Society of Nephrology 2013-10, Vol.24 (10), p.1529-1536
• Main Authors: KIM, Myung-Gyu, TAI YEON KOO, SURH, Charles D, AHN, Curie, JAESEOK YANG, YAN, Ji-Jing, EUNWON LEE, KYU HYUN HAN, JONG CHEOL JEONG, HAN RO, BEOM SEOK KIM, JO, Sang-Kyung, KOOK HWAN OH
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - therapeutic use; Antigen-Antibody Complex - physiology; Biological and medical sciences; Brief Communications; Cell Differentiation - immunology; Drug Evaluation, Preclinical; Fibrosis; Interleukin-2 - immunology; Interleukin-2 - physiology; Kidney - immunology; Kidney - pathology; Male; Medical sciences; Mice; Mice, Inbred C57BL; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Renal Insufficiency - immunology; Renal Insufficiency - pathology; Renal Insufficiency - prevention & control; Renovascular diseases; Reperfusion Injury - immunology; Reperfusion Injury - pathology; Reperfusion Injury - prevention & control; T-Lymphocytes, Regulatory - drug effects; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - pathology
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/ASN.2012080784

Regulatory T cells (Tregs) can suppress immunologic damage in renal ischemia-reperfusion injury (IRI), but the isolation and ex vivo expansion of these cells for clinical application remains challenging. Here, we investigated whether the IL-2/anti-IL-2 complex (IL-2C), a mediator of Treg expansion, can attenuate renal IRI in mice. IL-2C administered before bilateral renal IRI induced Treg expansion in both spleen and kidney, improved renal function, and attenuated histologic renal injury and apoptosis after IRI. Furthermore, IL-2C administration reduced the expression of inflammatory cytokines and attenuated the infiltration of neutrophils and macrophages in renal tissue. Depletion of Tregs with anti-CD25 antibodies abrogated the beneficial effects of IL-2C. However, IL-2C-mediated renal protection was not dependent on either IL-10 or TGF-β. Notably, IL-2C administered after IRI also enhanced Treg expansion in spleen and kidney, increased tubular cell proliferation, improved renal function, and reduced renal fibrosis. In conclusion, these results indicate that IL-2C-induced Treg expansion attenuates acute renal damage and improves renal recovery in vivo, suggesting that IL-2C may be a therapeutic strategy for renal IRI.