title: Lack of oral tolerance in aging is due to sequential loss of Peyer's patch cell interactions.
abstract: Our past studies showed that Peyer's patches were required for the induction of oral tolerance to the protein antigen ovalbumin (OVA), but not to the hapten 2,4,6-trinitrobenzene sulfonic acid (TNBS). In the present study, the effects of immunosenescence on oral tolerance induction were assessed with these two toleragens. Significant reductions in OVA-specific serum IgG antibody and CD4(+) T cell responses to subsequent challenge were observed in OVA-fed, young adult mice. Importantly, these reduced anti-OVA antibody responses were associated with delayed-type hypersensitivity, and antigen-induced CD4(+) T(h)1- and T(h)2-type cytokine responses. On the other hand, aged mice fed OVA failed to develop oral tolerance. Thus, CD4(+) T cells from Peyer's patches produced selected T(h)2- but no T(h)1-type cytokines. The TNP-specific serum IgG antibody and T cell responses were significantly diminished by prior TNBS feeding in young adult, 6- to 8-month-old and 12- to 14-month-old, but not in senescent, 2-year-old mice. Finally, we have directly assessed dendritic cell subsets and T cell responses in Peyer's patches, and their function in tolerance induction was impaired at an earlier stage of life. These results suggest that lack of oral tolerance to the protein OVA during aging is the result of dysfunctional Peyer's patches.
authors.affiliation: Department of Microbiology, Immunobiology Vaccine Center, University of Alabama at Birmingham, 761 BBRB, 845 19th Street South, Birmingham, AL 35294-2170, USA.
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Kato
authors.forename: Kohtaro
authors.initials: K
authors.lastname: Fujihashi
authors.forename: Rie
authors.initials: R
authors.lastname: Kato
authors.forename: Taeko
authors.initials: T
authors.lastname: Dohi
authors.forename: Keiko
authors.initials: K
authors.lastname: Fujihashi
authors.forename: Yukari
authors.initials: Y
authors.lastname: Hagiwara
authors.forename: Kosuke
authors.initials: K
authors.lastname: Kataoka
authors.forename: Ryoki
authors.initials: R
authors.lastname: Kobayashi
authors.forename: Jerry R
authors.initials: JR
authors.lastname: McGhee
mesh_terms: D000375:Aging / Q000276:immunology*; D000818:Animals; D003713:Dendritic Cells / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology*; D007150:Immunohistochemistry; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D010581:Peyer's Patches / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014302:Trinitrobenzenesulfonic Acid / Q000276:immunology
chemical_list: D014302:Trinitrobenzenesulfonic Acid; D010047:Ovalbumin