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The Journal of Immunology, 1998, 160: 1687-1693.
Copyright © 1998 by The American Association of Immunologists

Lack of Orally Induced Systemic Unresponsiveness in IFN-{gamma} Knockout Mice1

Mi-Na Kweon*, Kohtaro Fujihashi*, John L. VanCott{dagger}, Kazuo Higuchi*, Masafumi Yamamoto*,{ddagger}, Jerry R. McGhee{dagger} and Hiroshi Kiyono2,*,{ddagger}

Departments of * Oral Biology and {dagger} Microbiology, The Immunobiology Vaccine Center, University of Alabama at Birmingham, Medical Center, Birmingham, AL 35294; and {ddagger} Department of Mucosal Immunology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka, Japan

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 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-{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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