T regulatory cells 1 inhibit a Th2-specific response in vivo.
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.
Cottrez
F
F
Institut National de la Santé et de la Recherche Médicale Unité 343 Hopital de l'Archet, Nice, France.
Hurst
S D
SD
Coffman
R L
RL
Groux
H
H
D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation*; D002460:Cell Line; D002999:Clone Cells / Q000637:transplantation; D016207:Cytokines / Q000096:biosynthesis; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D007073:Immunoglobulin E / Q000096:biosynthesis; D007165:Immunosuppression Therapy / Q000379:methods; D007274:Injections, Intraperitoneal; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation*; D018417:Th1 Cells / Q000145:classification / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism*
D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D007073:Immunoglobulin E; D010047:Ovalbumin