title: Intestinal commensal bacteria promote T cell hyporesponsiveness and down-regulate the serum antibody responses induced by dietary antigen.
abstract: Colonization of the gut by commensal bacteria modulates the induction of oral tolerance and allergy. However, how these intestinal bacteria modulate antigen-specific T cell responses induced by oral antigens remains unclear. In order to investigate this, we used germ-free (GF) ovalbumin (OVA)-specific T cell receptor transgenic (OVA23-3) mice. Conventional (CV) or GF mice were administered an OVA-containing diet. Cytokine production by CD4(+) cells from spleen (SP), mesenteric lymph nodes (MLN) and Peyer's patches (PP) was evaluated by ELISA, as was the peripheral antibody titer. T cell phenotype was assessed by flow cytometry. CD4(+) cells from the SP and MLN of CV and GF mice fed an OVA diet for 3 weeks produced significantly less IL-2 than the corresponding cells from mice receiving a control diet, suggesting that oral tolerance could be induced at the T cell level in the systemic and intestinal immune systems of both bacterial condition of mice. However, we also observed that the T cell hyporesponsiveness induced by dietary antigen was delayed in the systemic immune tissues and was weaker in the intestinal immune tissues of the GF mice. Intestinal MLN and PP CD4(+) T cells from these animals also produced lower levels of IL-10, had less activated/memory type CD45RB(low) cells, and expressed lower levels of CTLA-4 but not Foxp3 compared to their CV counterparts. Furthermore, GF mice produced higher serum levels of OVA-specific antibodies than CV animals. CD40L expression by SP CD4(+) cells from GF mice fed OVA was higher than that of CV mice. These results suggest that intestinal commensal bacteria promote T cell hyporesponsiveness and down-regulate serum antibody responses induced by dietary antigens through modulation of the intestinal and systemic T cell phenotype.
authors.affiliation: Food and Physiological Functions Laboratory, Department of Food Bioscience and Biotechnology, Nihon University, 1866 Kameino Fujisawa-shi, Kanagawa, 252-0880, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Tsuda
authors.forename: Akira
authors.initials: A
authors.lastname: Hosono
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Yanagibashi
authors.forename: Miran
authors.initials: M
authors.lastname: Kihara-Fujioka
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hachimura
authors.forename: Kikuji
authors.initials: K
authors.lastname: Itoh
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Hirayama
authors.forename: Kyoko
authors.initials: K
authors.lastname: Takahashi
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaminogawa
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood*; D000941:Antigens / Q000276:immunology; D004044:Dietary Proteins / Q000276:immunology*; D015536:Down-Regulation; D005512:Food Hypersensitivity / Q000209:etiology / Q000276:immunology; D005856:Germ-Free Life; D006801:Humans; D007422:Intestines / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000906:Antibodies; D000941:Antigens; D004044:Dietary Proteins; D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin