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Signaling Pathway1
Department of Immunology, University of Glasgow, Western Infirmary, Glasgow, United Kingdom
There is considerable evidence that regulatory cytokines play an
important role in mediating the systemic tolerance found after oral
administration of protein Ags. Although most existing work has focused
on cytokines such as IL-4, IL-10, and TGF-ß, recent evidence from TCR
transgenic systems suggests that the induction of oral tolerance is
accompanied by priming of Ag-specific IFN-
production. IFN- has
also been implicated as a mediator of T cell tolerance in other models
in vivo and in vitro, including that induced by aerosol administration
of protein. We show here that feeding tolerogenic doses of OVA primes
for IFN- production in the spleen of mice with a normal T cell
repertoire. However, depleting IFN- at the time of feeding OVA had
no effect on the induction of tolerance. In addition, tolerance was
induced normally in both IFN- receptor knockout
(IFN-R-/-) and IL-12 p40 knockout
(IL-12-/-) mice. This was the case for all components of
the systemic immune response and also with a variety of feeding
protocols, including those believed to induce distinct regulatory
mechanisms. We conclude that IL-12-dependent IFN--mediated
regulation does not play an essential role in oral
tolerance.
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