Pranita P Sarangi1, Bumseok Kim, Barry T Rouse. 1. Comparative and Experimental Medicine, College of Veterinary Medicine, University of Tennessee, Knoxville, Tennessee 37996, USA.
Abstract
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-gamma, 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 SSIEFARL peptide-specific CD8(+)IFN-gamma(+) 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.
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-CD3monoclonal 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-gamma, 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 SSIEFARL peptide-specific CD8(+)IFN-gamma(+) 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.
Authors: Kaustuv Banerjee; Shilpa Deshpande; Mei Zheng; Udayasankar Kumaraguru; Stephen P Schoenberger; Barry T Rouse Journal: Cell Immunol Date: 2002-10 Impact factor: 4.868