Role of Stat4-mediated signal transduction events in the generation of aggressor CD4+ T cells in herpetic stromal keratitis pathogenesis.
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.
Banerjee
Kaustuv
K
Comparative and Experimental Medicine, College of Veterinary Medicine, The University of Tennessee, Knoxville, TN 37916, USA.
Biswas
Partha S
PS
Rouse
Barry T
BT
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D018792:Encephalitis, Viral / Q000276:immunology / Q000473:pathology; D006566:Herpesviridae Infections / Q000276:immunology / Q000473:pathology; D018259:Herpesvirus 1, Human / Q000502:physiology; D016849:Keratitis, Herpetic / Q000276:immunology* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D016513:Mice, SCID; D050797:STAT4 Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology / Q000821:virology
D050797:STAT4 Transcription Factor; C494091:Stat4 protein, mouse