Involvement of STAT4 in IgG subtype switching and ocular HSV-1 replication in mice

PURPOSE: To assess the relative impact of elevated T-helper 2 (T(H)2)- and reduced T-Helper 1 (T(H)1)-dependent immune responses on ocular herpes simplex virus type 1 (HSV-1) infection. METHODS: Signal transducer and activator of transcription protein 4 knockout mice (BALB/c-STAT4(−/−)) and wild-type BALB/c control mice were immunized with avirulent HSV-1 strain KOS or were mock-immunized. Three weeks after the third immunization, neutralizing antibody titers were determined by plaque reduction assays. Following ocular infection with virulent HSV-1 strain McKrae, viral replication in the eye, blepharitis, corneal scarring (CS), survival, and immunoglobulin (Ig) isotypes in sera were determined. RESULTS: Vaccinated STAT4(−/−) and BALB/c mice contained significant and similar neutralizing antibody titers and were completely protected against HSV-1-induced death and CS. In contrast to vaccinated STAT4(−/−) mice, mock-vaccinated STAT4(−/−) mice had higher ocular HSV-1 titers than mock-vaccinated BALB/c mice on days 2–3 post-ocular infection. There were also significant differences in the levels of IgG2a, IgG2b, and IgG3 in the sera of STAT4(−/−) mice when compared to the control BALB/c mice. CONCLUSIONS: These results suggest that the absence of T(H)1 cytokine responses did alter protection against viral replication and IgG isotypes but not eye disease or survival.