High-dose oral tolerance prevents antigen-induced eosinophil recruitment into the mouse airways.
We have previously shown that antigen-induced eosinophil recruitment into the tissue of sensitized mice is mediated by CD4+ T cells and IL-5. To determine whether the induction of oral tolerance down-regulates antigen-induced eosinophil recruitment into the tissue, we studied the effect of oral administration of a protein antigen on antigen-induced eosinophil infiltration in the trachea of sensitized mice, on antigen-induced CD4+ T cell infiltration and IL-5 production in the airways, and on the in vitro production of IL-2, IL-4, IL-5 and IFN-gamma in spleen cells of the mice. Oral administration of a protein antigen in high doses inhibited antigen-induced eosinophil infiltration in the trachea and IgE antibody production in mice in an antigen-specific manner. The oral administration of antigen also suppressed both CD4+ T cell recruitment into the trachea and IL-5 levels in the bronchoalveolar lavage fluids of the mice after antigen inhalation. In vitro antigen-induced production of IL-2, IFN-gamma, IL-4 and IL-5 was decreased in spleen cells of antigen-fed mice, indicating the induction of both Th1 and Th2 cell tolerance in vivo. On the other hand, pretreatment with anti-transforming growth factor-beta antibody at the time of immunization with antigen had no significant effect on the inhibition of antigen-induced eosinophil recruitment and IgE antibody production in antigen-fed mice. Finally, antigen-specific CD4+ T cells were not deleted in TCR transgenic mice after antigen feeding by FACS analysis. Taken together, these results indicate that high-dose oral tolerance induces not only Th1 but also Th2 cell tolerance in vivo and thereby inhibits antigen-induced eosinophil recruitment into the tissue.
Nakao
A
A
Department of Internal Medicine II, Chiba University School of Medicine, Chiba City, Japan.
Kasai
M
M
Kumano
K
K
Nakajima
H
H
Kurasawa
K
K
Iwamoto
I
I
D000284:Administration, Oral; D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000187:drug effects* / Q000276:immunology*; D000939:Epitopes; D005260:Female; D007108:Immune Tolerance; D007114:Immunization; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000276:immunology; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014132:Trachea / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology
D000941:Antigens; D000939:Epitopes; D007378:Interleukins; D016212:Transforming Growth Factor beta; D012710:Serum Albumin, Bovine; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin