Mechanism of Regulatory T Cells During Allergen-Specific Immunotherapy: from the Past to Future

Abstract

Allergen-specific subcutaneous immunotherapy (SCIT) has been effective used for the treatment choice for allergic rhinitis and asthma. Although it is clear that SCIT reduces the symptoms of allergic disease and can alter the natural course of allergic disease, however, the basic immunologic mechanisms involved in the amelioration of the allergic symptoms are still unknown. Recent studies suggest that the induction of CD4+CD25+ Foxp3+ Treg cells and IL-10-secreting type 1 Treg cells might be associated with suppression of allergic responses in patients after successful SIT. IL-10 and TGF-β from CD4+ Treg cells have proven essential roles in the maintenance of immunological self-tolerance in the CD4+ T cell compartment and inhibit Th2 cytokines releasing and differentiation. Evidences suggest that the shift from Th2 to Th1 induced by SIT might be mediated by induction of the apoptosis in mite allergen-responder CD4+IL-4+ Th2 cells in asthmatic children. We noted a significant increase in CD8+Foxp3+ Treg cells population expressing intracellular IL-10 and granzyme B can be generated by continuous allergen stimulation following six months of SCIT. We further demonstrated that CD8+ Treg cells, but not CD4+ Treg cells, can enhance CD4+CD45ROhi+ cell apoptosis. TLR2 agonist stimulates endogenous CD4+CD25hi+ Treg cells to produce IL-10, and may support another mechanism for the treatment of allergic disease. Future perspectives are required to clarify the precise Treg subsets involved SIT and develop clinical efficacious and safer allergen vaccines by utilizing the Treg cells functions.