Dietary antigen-specific T-cell responses: switch from an interleukin-10-dominated response in normal mice to a T-helper 1 cytokine profile in Galphai2-deficient mice prior to colitis.
We investigated dietary antigen-specific T-cell responses in mesenteric lymph nodes (MLN) and Peyer's patches (PP) in noncolitic control mice as well as in colitis-prone mice prior to onset of histological active colitis. T cells were restimulated in vitro with constituents isolated from the mouse diet. Interestingly, MLN T cells of littermate G(alpha)i2+/- control mice responded to soya with high production of interleukin (IL)-10, but did not produce proinflammatory T-helper 1 (Th1) cytokines. Recall dietary antigen stimulation of G(alpha)i2+/- PP T cells did not result in increased IL-10 production above the spontaneous production in the absence of antigenic stimulation. In strong contrast, MLN T cells from precolitic G(alpha)i2-/- mice produced high levels of interferon-gamma (IFN-gamma) upon restimulation with soya, which could be abolished using a major histocompatibility complex class II-blocking antibody. In conclusion, the present study demonstrates that MLN T lymphocytes in normal healthy mice respond with a significantly increased production of the regulatory cytokine IL-10 on re-encounter with dietary proteins in vitro. In marked contrast precolitic G(alpha)i2-/- mice respond to dietary antigens with a Th1-dominated cytokine response in the mucosa, prior to onset of colitis, with excessive IFN-gamma production. These results suggest that aberrant immune responses to dietary antigens could contribute as a potential pathogenic mechanism in the onset of colitis in G(alpha)i2-deficient mice.
Bjursten
M
M
Department of Clinical Immunology, The Sahlgrenska Academy of Göteborg University, Göteborg, Sweden.
Hultgren Hörnquist
E
E
D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D000941:Antigens / Q000008:administration & dosage*; D003092:Colitis / Q000209:etiology* / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D004032:Diet; D005260:Female; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000172:deficiency / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000096:biosynthesis*; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010581:Peyer's Patches / Q000276:immunology; D011518:Proto-Oncogene Proteins / Q000172:deficiency / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology
D000485:Allergens; D019138:Antibodies, Blocking; D000941:Antigens; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D011518:Proto-Oncogene Proteins; D016753:Interleukin-10; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; C498016:Gnai2 protein, mouse