| Abstract: |
Ocular infection with herpes simplex virus (HSV) causes a vision-impairing inflammatory reaction called herpetic stromal keratitis. In murine models, herpetic stromal keratitis lesions appear to be immunopathologic, mediated by CD4+ T cells of Th1 phenotype. To provide insight about cytokine networks and signaling events involved in the development of aggressor CD4 + T cells, ocular HSV infection was followed in mice deficient in Stat4 (Stat4-/- mice), the signal transducer for the cytokine interleukin-12 (IL-12). After ocular HSV infection of Stat4-/- and control BALB/c mice, clinical, histologic, and immunologic analyses were carried out. Further, to evaluate the involvement of Stat4 in the development of this aggressor population, naive CD4+ T cells from Stat4-/- and BALB/c mice were adoptively transferred to C.B-17 SCID mice 1 day after corneal infection. Although Stat4-/- mice demonstrated increased susceptibility to lethal encephalitis and facial lesions, interestingly, these mice had less severe stromal keratitis in comparison to control animals. Adoptive transfer of naive CD4+ T cells from Stat4-/- mice failed to produce disease in infected SCID recipients. The data imply a significant role of Stat4-mediated signaling events in the generation of an aggressor CD4+ T cell population in stromal keratitis pathogenesis. © Mary Ann Liebert, Inc. |
| Keywords: |
signal transduction; controlled study; histopathology; nonhuman; animal cell; mouse; animals; mice; mice, knockout; animal tissue; mus; animal experiment; animal model; mice, scid; mice, inbred balb c; animalia; gamma interferon; cd4+ t lymphocyte; cd4-positive t-lymphocytes; murinae; simplexvirus; herpesvirus 1, human; t-lymphocyte subsets; cd4 antigen; herpes simplex virus 1; interleukin 12; scid mouse; immunopathogenesis; herpesviridae infections; stat4 protein; herpes simplex keratitis; encephalitis, viral; keratitis, herpetic; stat4 transcription factor
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