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This report evaluates the role of interaction between glucocorticoid-induced tumor necrosis factor receptor (GITR) and GITR ligand (GITR-L) in the immuno-inflammatory response to infection with herpes simplex virus (HSV). Both GITR and GITR-L were transiently upregulated after ocular HSV infection, on antigen-specific T cells and antigen-presenting cells, respectively, in the draining lymph node (DLN). In addition, virus-specific T-cell responses in the DLN and spleen were enhanced by anti-GITR antibody treatment, an outcome expected to result in more severe inflammatory lesions. Intriguingly, the treatment resulted in significantly diminished T-cell-mediated ocular lesions. The explanation for these findings was that anti-GITR antibody treatment caused a reduced production of ocular MMP-9, a molecule involved in ocular angiogenesis, an essential step in the pathogenesis of herpetic keratitis. Our results are the first observations to determine in vivo kinetics of GITR and GITR-L expression after virus infection, and they emphasize the role of GITR-GITR-L interaction to regulate virus-induced immuno-inflammatory lesions.

Original publication




Journal article


J Virol

Publication Date





11935 - 11942


Animals, Antibodies, Monoclonal, Antigen-Presenting Cells, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Carrier Proteins, Female, Glucocorticoid-Induced TNFR-Related Protein, Herpesvirus 1, Human, Keratitis, Herpetic, Kinetics, Matrix Metalloproteinase 9, Mice, Mice, Congenic, Mice, Inbred C57BL, Receptors, Nerve Growth Factor, Receptors, Tumor Necrosis Factor, Tumor Necrosis Factors, Up-Regulation