Intestinal commensal bacteria promote T cell hyporesponsiveness and down-regulate the serum antibody responses induced by dietary antigen.
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.
Tsuda
Masato
M
Food and Physiological Functions Laboratory, Department of Food Bioscience and Biotechnology, Nihon University, 1866 Kameino Fujisawa-shi, Kanagawa, 252-0880, Japan.
Hosono
Akira
A
Yanagibashi
Tsutomu
T
Kihara-Fujioka
Miran
M
Hachimura
Satoshi
S
Itoh
Kikuji
K
Hirayama
Kazuhiro
K
Takahashi
Kyoko
K
Kaminogawa
Shuichi
S
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*
D000906:Antibodies; D000941:Antigens; D004044:Dietary Proteins; D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin