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

• Published in: The Journal of immunology (1950) Vol. 160; no. 4; pp. 1687 - 1693
• Main Authors: Kweon, M N, Fujihashi, K, VanCott, J L, Higuchi, K, Yamamoto, M, McGhee, J R, Kiyono, H
• Format: Journal Article
• Language: English
• Published: United States 15.02.1998
• Subjects: Administration, Oral; Animals; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Cytokines - biosynthesis; Dose-Response Relationship, Immunologic; Immune Tolerance - genetics; Immunity, Mucosal - genetics; Immunoglobulin G - biosynthesis; Immunoglobulin G - classification; Interferon-gamma - deficiency; Interferon-gamma - genetics; Interferon-gamma - immunology; Lymphocyte Activation - genetics; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Ovalbumin - administration & dosage; Ovalbumin - immunology; Spleen - cytology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.160.4.1687

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.