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

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 excessi ve Ags intruding through the airway mucosa induce a subset of regulatory CD 4(+) T cells secreting TGF-beta in the regional mediastinal lymph nodes (ML Ns), which inhibits Th2 cells and subsequent eosinophilic inflammation in t he trachea. In the present experiments we examined whether and in what mech anisms TGF-beta -secreting CD4(+) T cells in the MLNs regulate Th cell-medi ated skin inflammation using a previously established murine model. Th1 or Th2 cells injected s.c. into ear lobes of naive mice induced swelling, wher eas the concomitant local injection of MLN cells suppressed the inflammatio n. 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-indu ced inflammation and only partially in Th2-induced inflammation. rIL-10 red uced Th-induced ear swelling, although higher doses of rIL-10 were required in Th2-induced one. Thus, allergen-specific TGF-beta -producing CD4(+) T c ells induced in the respiratory tract controlled cutaneous inflammatory res ponses by Th1 or Th2 cells either directly by TGF-beta or indirectly throug h IL-10 induction. From a clinical standpoint, these observations might exp lain the mechanism of spontaneous regression in some patients with atopic d ermatitis, which exhibits both Th1- and Th2-mediated skin inflammation in r esponse to airborne protein Ags.