title: Naturally occurring lung CD4(+)CD25(+) T cell regulation of airway allergic responses depends on IL-10 induction of TGF-beta.
abstract: Peripheral tolerance to allergens is mediated in large part by the naturally occurring lung CD4(+)CD25(+) T cells, but their effects on allergen-induced airway responsiveness have not been well defined. Intratracheal, but not i.v., administration of naive lung CD4(+)CD25(+) T cells before allergen challenge of sensitized mice, similar to the administration of the combination of rIL-10 and rTGF-beta, resulted in reduced airway hyperresponsiveness (AHR) and inflammation, lower levels of Th2 cytokines, higher levels of IL-10 and TGF-beta, and less severe lung histopathology. Significantly, CD4(+)CD25(+) T cells isolated from IL-10(-/-) mice had no effect on AHR and inflammation, but when incubated with rIL-10 before transfer, suppressed AHR, and inflammation, and was associated with elevated levels of bronchoalveolar lavage TGF-beta levels. By analogy, anti-TGF-beta treatment reduced regulatory T cell activity. These data identify naturally occurring lung CD4(+)CD25(+) T cells as capable of regulating lung allergic responses in an IL-10- and TGF-beta-dependent manner.
authors.affiliation: Department of Pediatrics, Division of Cell Biology, National Jewish Medical and Research Center, Denver, CO 80206, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Joetham
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Takeda
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Takada
authors.forename: Christian
authors.initials: C
authors.lastname: Taube
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Miyahara
authors.forename: Shigeki
authors.initials: S
authors.lastname: Matsubara
authors.forename: Satoko
authors.initials: S
authors.lastname: Matsubara
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Koya
authors.forename: Yeong-Ho
authors.initials: YH
authors.lastname: Rha
authors.forename: Azzeddine
authors.initials: A
authors.lastname: Dakhama
authors.forename: Erwin W
authors.initials: EW
authors.lastname: Gelfand
mesh_terms: D000818:Animals; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D006967:Hypersensitivity / Q000188:drug therapy*; D007249:Inflammation / Q000188:drug therapy; D016753:Interleukin-10 / Q000172:deficiency / Q000502:physiology*; D008168:Lung / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000494:pharmacology
chemical_list: D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D016753:Interleukin-10