Targeting human CD2 by the monoclonal antibody CB.219 reduces intestinal inflammation in a humanized transfer colitis model

https://doi.org/10.1016/j.clim.2015.01.004Get rights and content
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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.

Abbreviations

CCL
CC chemokine ligand
CXCL
CXC-motif ligand
FoxP3
forkhead box protein 3
hpf
high power field
huCD2tg
mice expressing human CD2
IBD
inflammatory bowel diseases
IFNγ
interferon γ
Ig
immunoglobulin
IL
interleukin
LPL
lamina propria lymphocytes
PBS
phosphate-buffered saline
Rag1-ko
recombination activating gene 1-deficient
TGFβ
transforming growth factor β
TNFα
tumor necrosis factor α
Treg
regulatory T cells

Keywords

Human CD2
IBD mouse model
Transfer colitis
Monoclonal antibody CB.219
Reduced intestinal inflammation

Cited by (0)

1

Present address: Immatics Biotechnologies GmbH, Paul-Ehrlich-Straße 15, Tübingen D-72076, Germany.

2

Present address: Cold Spring Harbor Laboratory, One Bungtown Road, Cold Spring Harbor, New York 11724, USA.

3

Present address: Pathotres Joint Practice for Pathology, Teltowkanalstraße 2, Berlin D-12247, Germany.