title: The effects of Foxp3-expressing regulatory T cells expanded with CD28 superagonist antibody in DSS-induced mice colitis.
abstract: Regulatory T (Treg) cells play an important role in the pathogenesis of inflammatory bowel disease (IBD). In the present study, we found that a superagonistic CD28-specific monoclonal antibody (supCD28mAb, D665) could preferentially stimulate expansion of CD4+Foxp3+ Treg cells. Foxp3(EGFP) mice were orally administrated with 3.5% DSS for 5days, and intraperitoneally injected supCD28mAb 1mg/mice in treated group. All of the mice were sacrificed on day 8, and both clinical and histological parameters showed that the severity of colitis was significantly reduced in treated group compared to controls. In treated group, the proportion of CD103, CD152 and CD62L expression on Foxp3+Treg cells in the spleen and mesenteric lymph node were higher than controls. Furthermore, qRT-PCR analysis showed that expression of anti-inflammatory cytokines such as IL-10, TGF-β was significantly increased in treated group. Taken together, our data demonstrated that supCD28mAb targets CD4+Foxp3+Treg cells expansion in vivo, maintains and enhances their regulatory functions, to reduce the damage of colon in dextran sulfate sodium (DSS)-induced mouse colitis by secreting a large amount of IL-10. It represents a major advance towards the therapeutic use of polyclonally activated Treg cells as cellular therapy for treatment of IBD.
authors.affiliation: Department of Gastroenterology, Huashan Hospital, Fudan University, Shanghai, China; Division for Radiation Safety and Immune Tolerance, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Jiajie
authors.initials: J
authors.lastname: Chen
authors.forename: Lin
authors.initials: L
authors.lastname: Xie
authors.forename: Sayaka
authors.initials: S
authors.lastname: Toyama
authors.forename: Thomas
authors.initials: T
authors.lastname: Hünig
authors.forename: Shiro
authors.initials: S
authors.lastname: Takahara
authors.forename: Xiao-Kang
authors.initials: XK
authors.lastname: Li
authors.forename: Liang
authors.initials: L
authors.lastname: Zhong
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D018106:CD28 Antigens / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000503:physiopathology; D016264:Dextran Sulfate / Q000008:administration & dosage; D004195:Disease Models, Animal; D018450:Disease Progression; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000628:therapy; D016753:Interleukin-10 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D018106:CD28 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D016264:Dextran Sulfate