title: IL-2/anti-IL-2 complexes ameliorate lupus nephritis by expansion of CD4+CD25+Foxp3+regulatory T cells.
abstract: Adoptive transfer of regulatory T cells (Tregs) can delay disease progression and reduce mortality in lupus-prone mice. Here, we tested whether complex (IL-2C) consisting of IL-2 and anti-IL-2 monoclonal antibody (JES6-1) ameliorates lupus nephritis by expanding Tregs as an alternative to problematic Treg infusion therapy. IL-2C treatment of NZB/W F1 mice induced an effective and sustained expansion of CD4+CD25+Foxp3+Tregs in both the kidneys and spleen along with decreased renal infiltration of T cells, B cells, and innate immune cells. Compared with controls, mice treated with IL-2C showed reduced proteinuria and fewer acute and chronic renal pathological lesions with improved renal function and survival. IL-2C significantly attenuated glomerular and tubular injury, vasculitis scores, and renal deposition of IgG and C3. Disease activity markers, such as high levels of anti-dsDNA antibodies and immunoglobulin levels, and low levels of complement were improved in sera of IL-2C-treated mice. IL-2C treatment decreased renal expression of TNF-α and IL-6, and the frequencies of IFN-γ+CD4+and IL-17A+CD4+T cells in both the kidneys and spleen. Depletion of Tregs by anti-CD25 antibodies abrogated the beneficial effects of IL-2C. When compared with combination therapy of steroid and mycophenolate mofetil, IL-2C treatment showed similar or better outcomes. Thus, IL-2C protected lupus-prone mice against lupus nephritis by expanding Tregs. Hence, IL-2C could have therapeutic potential in lupus nephritis.
authors.affiliation: Transplantation Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Ji-Jing
authors.initials: JJ
authors.lastname: Yan
authors.affiliation: Transplantation Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Jae-Ghi
authors.initials: JG
authors.lastname: Lee
authors.affiliation: Transplantation Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Joon Young
authors.initials: JY
authors.lastname: Jang
authors.affiliation: Transplantation Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; Transplantation Center, Seoul National University Hospital, Seoul, Republic of Korea.
authors.forename: Tai Yeon
authors.initials: TY
authors.lastname: Koo
authors.affiliation: Transplantation Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors.forename: Curie
authors.initials: C
authors.lastname: Ahn
authors.affiliation: Transplantation Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea; Transplantation Center, Seoul National University Hospital, Seoul, Republic of Korea; Department of Surgery, Seoul National University Hospital, Seoul, Republic of Korea. Electronic address: jcyjs@dreamwiz.com.
authors.forename: Jaeseok
authors.initials: J
authors.lastname: Yang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D008181:Lupus Nephritis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D051379:Mice; D011507:Proteinuria / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D020127:Recovery of Function; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit
keywords: interleukin-2/anti-interleukin-2 complex; lupus nephritis; regulatory T cells