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

F Cottrez, SD Hurst, RL Coffman… - The Journal of …, 2000 - journals.aai.org
F Cottrez, SD Hurst, RL Coffman, H Groux
The Journal of Immunology, 2000journals.aai.org
We recently described a new population of CD4+ regulatory T cells (Tr1) that inhibits
proliferative responses of bystander T cells and prevents colitis induction in vivo through the
secretion of IL-10. IL-10, which had been primarily described as a Th2-specific cytokine
inhibiting Th1 responses, has displayed in several models a more general immune
suppression on both types of effector T cell responses. Using an immediate hypersensitivity
model in which BALB/c mice immunized with OVA (alum) normally generate Th2-dominated …
Abstract
We recently described a new population of CD4+ regulatory T cells (Tr1) that inhibits proliferative responses of bystander T cells and prevents colitis induction in vivo through the secretion of IL-10. IL-10, which had been primarily described as a Th2-specific cytokine inhibiting Th1 responses, has displayed in several models a more general immune suppression on both types of effector T cell responses. Using an immediate hypersensitivity model in which BALB/c mice immunized with OVA (alum) normally generate Th2-dominated responses, we examined the ability of OVA-specific Tr1 T cell clones to inhibit OVA-specific cytokines and Ab responses. In contrast to Th2 or Th1 T cell clones, transfer of Tr1 T cell clones coincident with OVA immunization inhibited Ag-specific serum IgE responses, whereas IgG1 and IgG2a synthesis were not affected. This specific inhibition was mediated in part through IL-10 secretion as anti-IL-10 receptor Abs treatment reverted the inhibitory effect of Tr1 T cell clones. Although specifically targeted to IgE responses, Tr1 clones’ inhibitory effects were more profound as they affected 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 prevent allergic disorders.
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