Interferon gamma induction during oral tolerance reduces T-cell migration to sites of inflammation.
OBJECTIVE
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.
Lee
H O
HO
Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Medical School, Chicago, Illinois, USA.
Miller
S D
SD
Hurst
S D
SD
Tan
L J
LJ
Cooper
C J
CJ
Barrett
T A
TA
D000284:Administration, Oral; D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D002465:Cell Movement / Q000502:physiology; D002645:Chickens; D016654:Genes, RAG-1 / Q000235:genetics; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000473:pathology; D007108:Immune Tolerance / Q000187:drug effects / Q000502:physiology*; D007249:Inflammation / Q000503:physiopathology*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D007958:Leukocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic / Q000235:genetics; D009055:Mouth / Q000276:immunology*; D010047:Ovalbumin / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000502:physiology*
D000911:Antibodies, Monoclonal; D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma; D010047:Ovalbumin