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Knockout Mice1




Departments of
*
Oral Biology and
Microbiology, The Immunobiology Vaccine Center, University of Alabama at Birmingham, Medical Center, Birmingham, AL 35294; and
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-
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-
-deficient (IFN-
-/-) 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-
-/- 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-
+/+ mice. In addition,
OVA-specific T cells from IFN-
-/- 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-
in the induction and maintenance of
mucosally induced tolerance.
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