XXXX and Regulatory T Cells Cooperate in Allergen-Specific Immunotherapy To Ameliorate @entity56 .

@entity1 @entity32 @entity19 @entity565 @entity102 @entity1618 @entity56 @entity3744
UNASSIGNED: @entity1 studies demonstrated that allergen-specific immunotherapy (IT) represents an effective treatment for @entity56 . IT involves repeated administration of the sensitizing allergen, indicating a crucial contribution of T cells to its medicinal benefit. However, the underlying mechanisms of IT, especially in a @entity102 , are far from being definitive. In the current study, we sought to elucidate the suppressive mechanisms of IT in a @entity19 model of @entity56 . OVA-sensitized @entity19 were challenged with OVA or PBS for 4 wk. After development of @entity32 , @entity19 received OVA-specific IT or placebo alternately to airway challenge for 3 wk. To analyze the T cell-mediated mechanisms underlying IT in vivo, we elaborated the role of T-bet-expressing Th1 cells, T cell-derived @entity1618 , and Ag-specific thymic as well as peripherally induced @entity3744 (+) regulatory T (Treg) cells. IT ameliorated airway hyperresponsiveness and @entity32 in a chronic @entity565 model. Of note, IT even resulted in a regression of structural changes in the airways following chronic inhaled allergen exposure. Concomitantly, IT induced Th1 cells, @entity3744 (+), and @entity1618 -producing Treg cells. Detailed analyses revealed that thymic Treg cells crucially contribute to the effectiveness of IT by promoting @entity1618 production in @entity3744 -negative T cells. Together with the peripherally induced Ag-specific @entity3744 (+) Treg cells, thymic @entity3744 (+) Treg cells orchestrate the curative mechanisms of IT. Taken together, we demonstrate that IT is effective in a chronic @entity56 and dependent on @entity1618 and thymic as well as peripherally induced Ag-specific Treg cells.
