title: CD3 mAb treatment ameliorated the severity of the cGVHD-induced lupus nephritis in mice by up-regulation of Foxp3+ regulatory T cells in the target tissue: kidney.
abstract: Teff/Treg imbalance orchestrated the onset and the progression of the lupus nephritis in a DBA/2→B6D2F1 murine model with cGVHD. In this paper, we first used 145-2C11 Ab to treat these human SLE-like diseased animals. The results showed that short-term low-dose anti-CD3 antibody treatment induced a significant remission of established proteinuria, production of autoantibodies, immune complex deposition and renal parenchyma lesions in lupus nephritic mice. Of note, we found a robust up-regulation of Foxp3 mRNA expression in the target tissue: kidney from mice with anti-CD3 antibody treatment compared to those with control IgG treatment. Likewise, an increased renal mRNA abundance for IL-10 was also observed in anti-CD3 antibody treated mice. In contrast, genes associated with inflammation and fibrosis as well as cytokines related to effector T cell responses were down-regulated by anti-CD3 mAb treatment. These findings suggested that short-term low-dose anti-CD3 antibody treatment might induced an IL-10-secreting Foxp3(+) regulatory T cells in this cGVHD target tissue: kidney, that suppressed the activation of effector T cells (Th1, Th2 and Th17), thus ameliorating the severity of the lupus nephritis in mice.
authors.affiliation: Department of Biomedicine, Institute of Frontier Medical Sciences, Jilin University, Changchun, China.
authors.forename: Ji-Lu
authors.initials: JL
authors.lastname: Zhang
authors.forename: De-Jun
authors.initials: DJ
authors.lastname: Sun
authors.forename: Chun-Mei
authors.initials: CM
authors.lastname: Hou
authors.forename: Ying-Lin
authors.initials: YL
authors.lastname: Wei
authors.forename: Xin-Ying
authors.initials: XY
authors.lastname: Li
authors.forename: Zu-Yin
authors.initials: ZY
authors.lastname: Yu
authors.forename: Jian-Nan
authors.initials: JN
authors.lastname: Feng
authors.forename: Bei-Fen
authors.initials: BF
authors.lastname: Shen
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: He
authors.initials: H
authors.lastname: Xiao
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D017252:CD3 Complex / Q000276:immunology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018450:Disease Progression; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D006086:Graft vs Host Disease / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D006801:Humans; D007165:Immunosuppression Therapy; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology / Q000503:physiopathology; D051379:Mice; D008811:Mice, Inbred DBA; D011507:Proteinuria; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation
chemical_list: D000911:Antibodies, Monoclonal; D017252:CD3 Complex; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D016753:Interleukin-10