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Originally published In Press as doi:10.1167/iovs.07-1638 on August 8, 2008
 (Investigative Ophthalmology and Visual Science. 2008;49:5425-5433.)
© 2008 by The Association for Research in Vision and Ophthalmology, Inc.
DOI:  10.1167/iovs.07-1638
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Non-mitogenic Anti-CD3F(ab')2 Monoclonal Antibody: A Novel Approach to Control Herpetic Stromal Keratitis

Pranita P. Sarangi,1 Bumseok Kim,2 and Barry T. Rouse1

1From the Comparative and Experimental Medicine, College of Veterinary Medicine, University of Tennessee, Knoxville, Tennessee; and 2Department of Pathology, College of Veterinary Medicine, Chonbuk National University, Chonju, South Korea.

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.






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