T regulatory cells 1 inhibit a Th2-specific response in vivo

We recently described a new population of CD4(+) regulatory T cells (Tr1) t hat inhibits proliferative responses of bystander T cells and prevents coli tis induction in vivo through the secretion of IL-10, IL-10, which had been primarily described as a Th2-specific cytokine inhibiting Th1 responses, h as displayed in several models a more general immune suppression on both ty pes of effector T cell responses. Using an immediate hypersensitivity model in which BALB/c mice immunized with OVA. (alum) normally generate Th2-domi nated responses, me examined the ability of OVA-specific Tr1 T cell clones to inhibit OVA-specific cytokines and Ab responses. In contrast to Th2 or T h1 T cell clones, transfer of Tr1 T cell clones coincident with OVA immuniz ation inhibited Ag-specific serum IgE responses, whereas IgG1 and IgG2a syn thesis were not affected. This specific inhibition was mediated in part thr ough IL-10 secretion as anti-IL-10 receptor Abs treatment reverted the inhi bitory effect of Tr1 T cell clones. Although specifically targeted to IgE r esponses, Tr1 clones' inhibitory effects mere more profound as they affecte d Ag-specific Th2 cell priming both in term of proliferative responses and cytokine secretion. These results suggest that regulatory T cells may play a fundamental role in maintaining the balance of the immune system to preve nt allergic disorders.