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

Background & Aims: Previous data suggest that oral antigen induces interferon (IFN)-gamma production in intestinal T cells. However, oral tolerance is associated with decreased production of IFN-gamma by T cells after antigen sensitization. The aim of this study was to examine the role of IFN-gamma, in oral tolerance. Methods: Oral tolerance was examined in BALB/c mice after the adoptive transfer of T cells from chicken ovalbumin (OVA(323-339))- specific, DO11.10 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-gamma 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-gamma prevented tolerance of DTH responses. Analysis of transgenic T-cell numbers in DTH sites by immunohistochemical staining suggested that induction of IFN-gamma by oral antigen decreased accumulation of transgenic T cells in cutaneous sites of antigen injection. IFN-gamma-deficient or wild-type DO11,10 and BALB/c mice were used to show that IFN-gamma production by donor transgenic T cells was critical for oral tolerance. Conclusions: These data suggest that the induction of IFN-gamma by oral antigen contributes to systemic tolerance by decreasing migration of T cells to peripheral sites of inflammation.