title: IL-2/anti-IL-2 complex attenuates renal ischemia-reperfusion injury through expansion of regulatory T cells.
abstract: 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.
authors.affiliation: Transplantation Center, Seoul National University Hospital, Seoul;
authors.forename: Myung-Gyu
authors.initials: MG
authors.lastname: Kim
authors.forename: Tai Yeon
authors.initials: TY
authors.lastname: Koo
authors.forename: Ji-Jing
authors.initials: JJ
authors.lastname: Yan
authors.forename: Eunwon
authors.initials: E
authors.lastname: Lee
authors.forename: Kyu Hyun
authors.initials: KH
authors.lastname: Han
authors.forename: Jong Cheol
authors.initials: JC
authors.lastname: Jeong
authors.forename: Han
authors.initials: H
authors.lastname: Ro
authors.forename: Beom Seok
authors.initials: BS
authors.lastname: Kim
authors.forename: Sang-Kyung
authors.initials: SK
authors.lastname: Jo
authors.forename: Kook Hwan
authors.initials: KH
authors.lastname: Oh
authors.forename: Charles D
authors.initials: CD
authors.lastname: Surh
authors.forename: Curie
authors.initials: C
authors.lastname: Ahn
authors.forename: Jaeseok
authors.initials: J
authors.lastname: Yang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000936:Antigen-Antibody Complex / Q000502:physiology*; D002454:Cell Differentiation / Q000276:immunology*; D004353:Drug Evaluation, Preclinical; D005355:Fibrosis; D007376:Interleukin-2 / Q000276:immunology / Q000502:physiology*; D007668:Kidney / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051437:Renal Insufficiency / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D015427:Reperfusion Injury / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D007376:Interleukin-2