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Induction of Intestinal Inflammation by Adoptive Transfer of CBir1 TCR Transgenic CD4+ T Cells to Immunodeficient Mice
Published on: December 16, 2021
Targeting human CD2 by the monoclonal antibody CB.219 reduces intestinal inflammation in a humanized transfer colitis
Ulrike Erben1, Nina N Pawlowski1, Katja Doerfel1
1Department of Medicine I-Gastroenterology, Infectious Diseases and Rheumatology and Research Center ImmunoSciences, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, Berlin D-12203, Germany.
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.
Insights
Monoclonal antibodies targeting CD2 on T cells effectively reduced intestinal inflammation in a humanized colitis model. This suggests a promising new therapeutic strategy for treating colitis and related inflammatory conditions.
Area of Science:
- Immunology
- Gastroenterology
- Inflammation Research
Background:
- The cell adhesion molecule CD2 plays a role in T-cell activation.
- CD2 deficiency or blockade has shown promise in reducing intestinal inflammation in animal models.
Purpose of the Study:
- To evaluate the therapeutic potential of monoclonal antibodies (mAbs) targeting human CD2 in colitis treatment.
- To investigate the efficacy of anti-human CD2 mAb CB.219 in a humanized mouse model of colitis.
Main Methods:
- Induction of transfer colitis in a humanized mouse model using naïve CD4(+) T cells expressing human CD2.
- Treatment with anti-human CD2 mAb CB.219 in both preventive and therapeutic regimens.
- Assessment of intestinal tissue damage, pro-inflammatory cytokine production, and immune cell infiltration.
Main Results:
- The mAb CB.219 demonstrated protective effects against severe colitis in a preventive setting.
- Therapeutic treatment with CB.219 ameliorated existing intestinal inflammation.
- Reduced tissue damage was associated with suppressed pro-inflammatory cytokine production by lamina propria lymphocytes and decreased infiltration of macrophages and T cells.
Conclusions:
- Targeting CD2 on T cells with mAb CB.219 offers a novel therapeutic approach for colitis.
- This strategy significantly reduces intestinal inflammation and immune cell infiltration in a humanized model.
- Further investigation into CD2-targeted therapies for inflammatory bowel diseases is warranted.
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