Interferon gamma induction during oral tolerance reduces T-cell migration to sites of inflammation

Background and Aims: Previous data suggest that oral antigen induces interferon (IFN)-γ production in intestinal T cells. However, oral tolerance is associated with decreased production of IFN-γ by T cells after antigen sensitization. The aim of this study was to examine the role of IFN-γ in oral tolerance. Methods: Oral tolerance was examined in BALB/c mice after the adoptive transfer of T cells from chicken ovalbumin (OVA₃₂₃- ₃₃₉)specific, D011.10 x RAG-1(-/-) T-cell receptor transgenic mice. Results: OVA feeding induced systemic tolerance of delayed-type hypersensitivity (DTH) and antibody responses. OVA feeding up-regulated IFN- γ, production by transgenic T cells in Peyer's patch and mesenteric lymph node but not splenic tissues. Treatment of OVA-fed mice with neutralizing monoclonal antibody to IFN-γ, prevented tolerance of DTH responses. Analysis of transgenic T-cell numbers in DTH sites by immunohistochemical staining suggested that induction of IFN-γ by oral antigen decreased accumulation of transgenic T cells in cutaneous sites of antigen injection. IFN-γ-deficient or wild-type D011.10 and BALB/c mice were used to show that IFN-γ production by donor transgenic T cells was critical for oral tolerance. Conclusions: These data suggest that the induction of IFN-γ by oral antigen contributes to systemic tolerance by decreasing migration of T cells to peripheral sites of inflammation.