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Interleukin‐2/anti‐interleukin‐2 monoclonal antibody immune complex suppresses collagen‐induced arthritis in mice by fortifying interleukin‐2/ STAT 5 signalling pathways
Author(s) -
Lee SeonYeong,
Cho MiLa,
Oh HyeJwa,
Ryu JunGeol,
Park MinJung,
Jhun JooYeon,
Park MiKyung,
Stone John C.,
Ju JiHyun,
Hwang SueYun,
Park SungHwan,
Surh Charles D.,
Kim HoYoun
Publication year - 2012
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12008
Subject(s) - microbiology and biotechnology , immune system , interleukin , interleukin 2 , chemistry , splenocyte , immunology , il 2 receptor , stat protein , t cell , cytokine , biology , endocrinology , stat3 , medicine , signal transduction
Summary In this study, we investigated the effects of administration of interleukin‐2 ( IL ‐2)/ JES 6‐1 (anti‐ IL ‐2 monoclonal antibody) immune complexes on the expansion and activation of regulatory T ( T reg) cells, the down‐regulation of T helper type 17 ( T h17) cells, and the control of the severity of collagen‐induced arthritis ( CIA ). Wild‐type and CIA ‐induced wild‐type mice were injected intraperitoneally (i.p.) with IL ‐2 or IL ‐2/ JES 6‐1 complex three times at 2‐day intervals. Treg cell surface markers were analysed by flow cytometry. After injecting IL ‐2 or IL ‐2/ JES 6‐1, the time kinetics of IL ‐2 signalling molecules was examined by FACS and Western blotting. Concentrations of IL ‐17 and IL ‐10 were measured by ELISA . Injection of IL ‐2/ JES 6‐1 increased the proportion of F oxp3 + Treg cells among splenic CD 4 + T cells, which reached the highest level on day 4 after injection. Up‐regulation of CTLA 4, GITR and glycoprotein‐A repetitions predominant (GARP) was observed. Activation of p ‐signal transducer and activator of transcription 5 ( STAT 5) was apparent within 3 hr after injection of IL ‐2/ JES 6‐1 complexes. Expression of IL ‐2 signalling molecules, including p ‐ AKT and p ‐p38/mitogen‐activated protein kinase, was also higher in splenocytes treated with IL ‐2/ JES 6‐1 complexes. Injection of IL ‐2/ JES 6‐1 complexes suppressed the induction of CIA and the production of IL ‐17 and inflammatory responses while increasing the level of IL ‐10 in the spleen. The expansion of Treg cells (via STAT 5) and the concomitant increase in IL ‐2 signalling pathways by IL ‐2/ JES 6‐1 complexes suggests their potential use as a novel therapeutic agent for the treatment of autoimmune arthritis.