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Publication : Lack of orally induced systemic unresponsiveness in IFN-gamma knockout mice.

First Author  Kweon MN Year  1998
Journal  J Immunol Volume  160
Issue  4 Pages  1687-93
PubMed ID  9469425 Mgi Jnum  J:45665
Mgi Id  MGI:1195820 Doi  10.4049/jimmunol.160.4.1687
Citation  Kweon MN, et al. (1998) Lack of orally induced systemic unresponsiveness in IFN-gamma knockout mice. J Immunol 160(4):1687-93
abstractText  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-gamma 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-gamma-deficient (IFN-gamma-/-) 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- gamma-/- mice displayed a partial diminution 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-gamma+/+ mice. In addition, OVA-specific T cells from IFN-gamma-/- 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-gamma in the induction and maintenance of mucosally induced tolerance.
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