Non-mitogenic anti-CD3F(ab′)₂ monoclonal antibody: A novel approach to control herpetic stromal keratitis

PURPOSE. Treatment with anti-CD3 antibody has been shown to ameliorate and reverse an existing immunopathological condition by inducing tolerance. The purpose of this study is to assess the therapeutic potential of non-Fc receptor (FcR) binding anti-CD3 monoclonal antibody (mAb), CD3F(ab′)₂, for the treatment of herpes simplex virus (HSV)-induced stromal keratitis (SK). METHODS. Balb/c and C57BL/6 mice were ocularly infected with HSV-1 strain RE (HSV-1RE). Infected animals were treated with CD3F(ab′)₂. Development of SK starting from day 5 postinfection (p.i.), infiltration of inflammatory cells into the corneas and the generation of the immune response were compared with untreated animals using slit-lamp biomicroscopy, flow cytometry, and ELISA. RESULTS. In vivo administration of CD3F(ab′) ₂ resulted in significant reduction in the severity and incidence of SK in the infected animals compared to untreated counterparts. Infiltration of fewer pathogenic CD4⁺ T cells into the cornea, along with a lower percentage of cells that could be induced to express IFN-γ, occurred with anti-CD3F(ab′)₂ treatment. Similar observations were noted in the secondary lymphoid tissues. Additionally, an increase in the frequency of CD4⁺Foxp3⁺ regulatory T cells was noticed in both cornea and lymphoid tissues of treated animals compared to untreated animals. Treatment with CD3F(ab′)₂ also reduced the number of SSIE-FARL peptide-specific CD8⁺IFN-γ⁺ T cells in the secondary lymphoid tissues. Furthermore, use of this reagent was moderately effective in limiting lesions in mice with established lesions. CONCLUSIONS. Taken together, these results show that non-FcR binding anti-CD3 treatment could be useful in limiting SK lesions.