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The Journal of Immunology, 2000, 165: 4848-4853.
Copyright © 2000 by The American Association of Immunologists

T Regulatory Cells 1 Inhibit a Th2-Specific Response In Vivo1

Françoise Cottrez*, Steven D. Hurst{dagger}, Robert L. Coffman{dagger} and Hervé Groux2,*

* Institut National de la Santé et de la Recherche Médicale Unité 343 Hopital de l’Archet, Nice, France; and {dagger} DNAX Research Institute, Palo Alto, CA 94304

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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