TGF-beta induced by oral tolerance ameliorates experimental tracheal eosinophilia.
Induction of peripheral tolerance is one of the feasible approaches for the control of autoimmunities and allergies. Therapeutic applications of oral tolerance to autoimmunities are in progress both experimentally and clinically, while those to allergies have been poorly investigated. We examined the induction of CD4+ T cells with suppressive properties by oral tolerance and the mechanism by which these cells down-regulated Ag-induced eosinophilia in the trachea. Feeding of mice transgenic for anti-OVA TCR with high doses of OVA inhibited the airway eosinophilic 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 specificity of the suppressor T cells was documented by the failure of spleen cells from mice that were orally tolerant of OVA to suppress irrelevant Ag, KLH-specific airway eosinophilic inflammation. The suppressive effect of the transferred T cells on eosinophil recruitment was neutralized by anti-TGF-beta mAb, but not anti-IFN-gamma mAb, indicating that the suppression is due to the inhibitory effect by secreted TGF-beta, but not to the dominance of the transferred Th1 cells over Th2 cells. This is the first study to reveal a link between oral tolerance and the regulation of Th2-mediated experimental tracheal eosinophilia through TGF-beta. Our experimental model suggests possible therapeutic applications of oral tolerance for the treatment of allergic disorders such as bronchial asthma.
Haneda
K
K
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Sano
K
K
Tamura
G
G
Sato
T
T
Habu
S
S
Shirato
K
K
D019264:Adoptive Transfer; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004802:Eosinophilia / Q000276:immunology* / Q000473:pathology; D007108:Immune Tolerance; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D014132:Trachea / Q000276:immunology* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000276:immunology*
D000485:Allergens; D016212:Transforming Growth Factor beta