Targeting human CD2 by the monoclonal Antibody CB.219 reduces intestinal Inflammation in a humanized Transfer Colitis Model

The cell adhesion molecule CD2 facilitates antigen-independent T-cell activation. CD2 deficiency or blockade reduces intestinal inflammation in murine models. Transfer colitis induced by naúve CD4-positive T cells expressing human CD2 (huCD2 tg) was treated with different monoclonal antibodies (mAb) specific for human CD2. Only one of the mAb, the clone CB.219 protected from severe colitis in a preventive treatment regimen. More importantly, therapeutic treatment ameliorated intestinal inflammation. Diminished intestinal tissue damage was paralleled by a profound suppression of the capacity of lamina propria lymphocytes to produce proinflammatory cytokines and tumor necrosis factor α as well as the neutrophil chemoattractant CXC-motif ligand 1 and the CC-chemokine ligand 3. Consequently, the infiltration with macrophages and T cells in the colonic mucosal tissue was low. Proposing that CB.219 prevents activation of engrafted T cells, we tested the antibody in huCD2tg mice orally infected with Toxoplasma gondii. While CB.219 did not affect the fulminant ileum inflammation, hence does not hamper the response to the pathogen, treated animals showed low levels of interferon g mRNA. Strongly suggesting a therapeutic potential for CB.219 in colitis treatment, this human CD2 mAb does not generally interferes with T cell-mediated inflammations but more specifically with the inflammation of the colonic mucosa.