title: TGF-beta-producing CD4+ mediastinal lymph node cells obtained from mice tracheally tolerized to ovalbumin (OVA) suppress both Th1- and Th2-induced cutaneous inflammatory responses to OVA by different mechanisms.
abstract: Advances in the treatment of allergic disorders require elucidation of the autoregulatory immune systems induced in averting detrimental inflammatory responses against invading foreign Ags. We previously reported that excessive Ags intruding through the airway mucosa induce a subset of regulatory CD4+ T cells secreting TGF-beta in the regional mediastinal lymph nodes (MLNs), which inhibits Th2 cells and subsequent eosinophilic inflammation in the trachea. In the present experiments we examined whether and in what mechanisms TGF-beta-secreting CD4+ T cells in the MLNs regulate Th cell-mediated skin inflammation using a previously established murine model. Th1 or Th2 cells injected s.c. into ear lobes of naive mice induced swelling, whereas the concomitant local injection of MLN cells suppressed the inflammation. The suppressor activities of MLN cells were markedly neutralized by anti-TGF-beta mAb and were mimicked by rTGF-beta. The MLN cell- and rTGF-beta-induced inhibition was reversed by anti-IL-10 mAb significantly in Th1-induced inflammation and only partially in Th2-induced inflammation. rIL-10 reduced Th-induced ear swelling, although higher doses of rIL-10 were required in Th2-induced one. Thus, allergen-specific TGF-beta-producing CD4+ T cells induced in the respiratory tract controlled cutaneous inflammatory responses by Th1 or Th2 cells either directly by TGF-beta or indirectly through IL-10 induction. From a clinical standpoint, these observations might explain the mechanism of spontaneous regression in some patients with atopic dermatitis, which exhibits both Th1- and Th2-mediated skin inflammation in response to airborne protein Ags.
authors.affiliation: Department of Dermatology, Tohoku University School of Medicine, Seiryo-machi 101, Aoba-ku, Sendai 980-8574, Japan. terui@mail.cc.tohoku.ac.jp
authors.forename: T
authors.initials: T
authors.lastname: Terui
authors.forename: K
authors.initials: K
authors.lastname: Sano
authors.forename: H
authors.initials: H
authors.lastname: Shirota
authors.forename: N
authors.initials: N
authors.lastname: Kunikata
authors.forename: M
authors.initials: M
authors.lastname: Ozawa
authors.forename: M
authors.initials: M
authors.lastname: Okada
authors.forename: M
authors.initials: M
authors.lastname: Honda
authors.forename: G
authors.initials: G
authors.lastname: Tamura
authors.forename: H
authors.initials: H
authors.lastname: Tagami
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D002478:Cells, Cultured; D003872:Dermatitis / Q000276:immunology*; D003876:Dermatitis, Atopic / Q000276:immunology; D007108:Immune Tolerance; D016753:Interleukin-10 / Q000494:pharmacology; D008198:Lymph Nodes / Q000276:immunology*; D008297:Male; D008482:Mediastinum; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000637:transplantation; D018418:Th2 Cells / Q000276:immunology / Q000637:transplantation; D014132:Trachea; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000494:pharmacology*
chemical_list: D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D010047:Ovalbumin