TGF-β-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

T. Terui, K. Sano, H. Shirota, N. Kunikata, M. Ozawa, M. Okada, M. Honda, G. Tamura, H. Tagami

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

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-β 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-β-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-β mAb and were mimicked by rTGF-β. The MLN cell- and rTGF-β-induced inhibition was reversed by anti-1L-10 mAb significantly in Th1-induced inflammation and only partially in Th2-induced inflammation. r1L-10 reduced Th-induced ear swelling, although higher doses of r1L-10 were required in Th2-induced one. Thus, allergen-specific TGF-β-producing CD4+ T cells induced in the respiratory tract controlled cutaneous inflammatory responses by Th1 or Th2 cells either directly by TGF-β 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.

Original languageEnglish
Pages (from-to)3661-3667
Number of pages7
JournalJournal of Immunology
Volume167
Issue number7
DOIs
Publication statusPublished - 2001 Oct 1

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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