Allergen-specific Th1 cells counteract efferent Th2 cell-dependent bronchial hyperresponsiveness and eosinophilic inflammation partly via IFN-gamma

Th2 T cell immune-driven inflammation plays an important role in allergic a sthma, We studied the effect of counterbalancing Th1 T cells in an asthma m odel in Brown Norway rats that favors Th2 responses. Rats received i.v. tra nsfers of syngeneic allergen-specific Th1 or Th2 cells, 24 h before aerosol exposure to allergen, and were studied 18-24 h later. Adoptive transfer of OVA-specific Th2 cells, but not Th1 cells, and OVA, but not BSA exposure, induced bronchial hyperresponsiveness (BHR) to acetylcholine and eosinophil ia in a cell number-dependent manner. Importantly, cotransfer of OVA-specif ic Th1 cells dose-dependently reversed BHR and bronchoalveolar lavage (BAL) eosinophilia, but not mucosal eosinophilia, OVA-specific Th1 cells transfe rred alone induced mucosal eosinophilia, but neither BHR nor BAL eosinophil ia. Th1 suppression of BHR and BAL eosinophilia was allergen specific, sinc e cotransfer of BSA-specific Th1 cells with the OVA-specific Th2 cells was not inhibitory when OVA aerosol alone was used, but was suppressive with OV A and BSA challenge, Furthermore, recipients of Th1 cells alone had increas ed gene expression for IFN-gamma in the Lungs, while those receiving Th2 ce lls alone showed increased IL-4 mRNA, Importantly, induction of these Th2 c ytokines was inhibited in recipients of combined Th1 and Th2 tells. Anti-IF N-gamma treatment attenuated the down-regulatory effect of Th1 cells. Aller gen-specific Th1 cells down-regulate efferent Th2 cytokine-dependent BHR an d BAL eosinophilia in an asthma model via mechanisms that depend on IFN-gam ma, Therapy designed to control the efferent phase of established asthma by augmenting down-regulatory Th1 counterbalancing mechanisms should be effec tive.