TGF-BETA INDUCED BY ORAL TOLERANCE AMELIORATES EXPERIMENTAL TRACHEAL EOSINOPHILIA

Induction of peripheral tolerance is one of the feasible approaches fo r the control of autoimmunities and allergies, Therapeutic application s of oral tolerance to autoimmunities are in progress both experimenta lly and clinically, while those to allergies have been poorly investig ated, We examined the induction of CD4(+) T cells with suppressive pro perties by oral tolerance and the mechanism by which these cells down- regulated Ag-induced eosinophilia in the trachea, Feeding of mice tran sgenic for anti-OVA TCR with high doses of OVA inhibited the airway eo sinophilic inflammation induced by the intratracheally administered Ag , This inhibition reflected the mechanism of active suppression, since the inhibitory effect was adoptively transferred by splenic CD4(+) T cells from the transgenic mice fed with high doses of OVA, The Ag spec ificity of the suppressor T cells was documented by the failure of spl een cells from mice that were orally tolerant of OVA to suppress irrel evant Bg, KLH-specific airway eosinophilic inflammation, The suppressi ve effect of the transferred T cells an eosinophil recruitment was neu tralized by anti-TGF beta mAb, but not anti-IFN-gamma mAb, indicating that the suppression is due to the inhibitory effect by secreted TGF-b eta, but: not to the dominance of the transferred Th1 cells over Th2 c ells, This is the first study is reveal a link between oral tolerance and the regulation of Th2-mediated experimental tracheal eosinophilia through TGF-P, Our experimental model suggests possible therapeutic ap plications of oral tolerance for the treatment of allergic disorders s uch as branchial asthma.