Non-mitogenic anti-CD3F(ab')2 monoclonal antibody: a novel approach to control herpetic stromal keratitis.
OBJECTIVE
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.
Sarangi
Pranita P
PP
Comparative and Experimental Medicine, College of Veterinary Medicine, University of Tennessee, Knoxville, Tennessee 37996, USA.
Kim
Bumseok
B
Rouse
Barry T
BT
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D017252:CD3 Complex / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003319:Corneal Stroma / Q000821:virology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D016849:Keratitis, Herpetic / Q000276:immunology / Q000517:prevention & control*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011971:Receptors, Immunologic / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology
D000911:Antibodies, Monoclonal; D017252:CD3 Complex; C052643:F(ab')2 receptor; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D011971:Receptors, Immunologic; D007371:Interferon-gamma