Lack of orally induced systemic unresponsiveness in IFN-γ knockout mice

Academic Article

Abstract

  • 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 number 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 as 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(-/-) ice 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.
  • Published In

    Author List

  • Kweon MN; Fujihashi K; VanCott JL; Higuchi K; Yamamoto M; McGhee JR; Kiyono H
  • Start Page

  • 1687
  • End Page

  • 1693
  • Volume

  • 160
  • Issue

  • 4