Lack of Orally Induced Systemic Unresponsiveness in IFN-γ Knockout Mice

Splenic T cells isolated from BALB/c mice that had been mucosally tolerized by oral administration of 25 mg of OVA revealed selective increases in IFN-γ production with impaired levels of IL-2, IL-4, IL-5, and IL-10. These mice possessed reduced splenic OVA-specific T cell proliferative and delayed-type hypersensitivity responses when compared with nontolerized controls. Further, OVA-specific IgG Ab responses in serum and the numbers of IgG Ab-forming cells in spleen were significantly diminished following systemic challenge with OVA in CFA. When IFN-γ-deficient (IFN-γ−/−) mice of the same genetic background were given an oral dose of 25 mg of OVA before systemic immunization, no reduction in OVA-specific IgG Ab responses in serum and spleen was seen. Furthermore, the serum IgG Ab responses were restricted to IgG1 and IgG2b subclasses. Interestingly, although IFN-γ−/− mice displayed a partial diminishment of T cell proliferative and delayed-type hypersensitivity responses to OVA, significant responses were still present when compared with the low responses noted in IFN-γ+/+ mice. In addition, OVA-specific T cells from IFN-γ−/− mice produced Th2-type cytokines (e.g., IL-4), which provided help for systemic OVA-specific serum IgG1 and IgG2b Ab responses. These findings clearly indicate a central role for IFN-γ in the induction and maintenance of mucosally induced tolerance.