title: Targeting human CD2 by the monoclonal antibody CB.219 reduces intestinal inflammation in a humanized transfer colitis model.
abstract: The cell adhesion molecule CD2 facilitates antigen-independent T-cell activation and CD2 deficiency or blockade reduces intestinal inflammation in murine models. We here aimed to evaluate the therapeutic potential of monoclonal antibodies (mAb) specific for human CD2 in colitis treatment. Transfer colitis induced by naïve CD4(+) T cells expressing human CD2 was treated with anti-human CD2 mAb. The mAb CB.219 protected from severe colitis in a preventive treatment regimen, while therapeutic treatment ameliorated intestinal inflammation. Diminished intestinal tissue damage was paralleled by a profound suppression of lamina propria lymphocytes to produce pro-inflammatory cytokines and tumor necrosis factor α as well as the neutrophil chemoattractant CXC motif ligand 1 and the CC chemokine ligand 3. Furthermore, infiltration with macrophages and T cells was low. Thus, reduced intestinal inflammation in our humanized colitis model by targeting CD2 on T cells with the mAb CB.219 suggests a novel approach for colitis treatment.
authors.affiliation: Department of Medicine I-Gastroenterology, Infectious Diseases and Rheumatology and Research Center ImmunoSciences, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, Berlin D-12203, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Erben
authors.affiliation: Department of Medicine I-Gastroenterology, Infectious Diseases and Rheumatology and Research Center ImmunoSciences, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, Berlin D-12203, Germany.
authors.forename: Nina N
authors.initials: NN
authors.lastname: Pawlowski
authors.affiliation: Department of Medicine I-Gastroenterology, Infectious Diseases and Rheumatology and Research Center ImmunoSciences, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, Berlin D-12203, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Doerfel
authors.affiliation: Institute of Pathology, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, Berlin D-12203, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Loddenkemper
authors.affiliation: Department of Medicine I, St. Marienkrankenhaus, Salzburger Straße 15, Ludwigshafen D-67067, Germany.
authors.forename: Jörg C
authors.initials: JC
authors.lastname: Hoffmann
authors.affiliation: Department of Medicine I-Gastroenterology, Infectious Diseases and Rheumatology and Research Center ImmunoSciences, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, Berlin D-12203, Germany.
authors.forename: Britta
authors.initials: B
authors.lastname: Siegmund
authors.affiliation: Department of Medicine I-Gastroenterology, Infectious Diseases and Rheumatology and Research Center ImmunoSciences, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, Berlin D-12203, Germany. Electronic address: anja.kuehl@charite.de.
authors.forename: Anja A
authors.initials: AA
authors.lastname: Kühl
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D018801:CD2 Antigens / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D015212:Inflammatory Bowel Diseases / Q000503:physiopathology / Q000628:therapy*; D007422:Intestines / Q000187:drug effects / Q000503:physiopathology*; D051379:Mice
chemical_list: D000911:Antibodies, Monoclonal; D018801:CD2 Antigens; D016207:Cytokines
keywords: Human CD2; IBD mouse model; Monoclonal antibody CB.219; Reduced intestinal inflammation; Transfer colitis