Nature Immunology5, 1149 - 1156 (2004)
Published online: 26 September 2004; | doi:10.1038/ni1122
Induction of T helper type 1−like regulatory cells that express Foxp3 and protect against airway hyper-reactivity
Philippe Stock1, 4, Omid Akbari1, 4, Gerald Berry2, Gordon J Freeman3, Rosemarie H DeKruyff1, 4
& Dale T Umetsu1, 4
1
Division of Immunology and Allergy, Department of Pediatrics, Stanford University, Stanford, California 94305-5208, USA.
2
Department of Pathology, Stanford University, Stanford, California 94305-5208, USA.
3
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
4
Present addresses: Department of Pediatric Pneumology and Immunology, University Hospital Charité, Augustenburger Platz 1, 13353 Berlin, Germany (P.S.) and Division of Immunology, Children's Hospital Boston, Karp Research Building, Harvard Medical School, Boston, Massachusetts 02115-5737, USA (O.A., R.H.D. and D.T.U.).
The range of regulatory T cell (TR cell) types that control immune responses is poorly understood. We describe here a population of TR cells that developed in vivo from naive CD4+CD25- T cells during a T helper type 1 (TH1)−polarized response, distinct from CD25+ TR cells. These antigen-specific TR cells were induced by CD8+ DCs, produced both interleukin 10 and interferon-, and potently inhibited the development of airway hyper-reactivity. These TR cells expressed the transcription factors Foxp3 and T-bet, indicating that these TR cells are related to TH1 cells. Thus, adaptive TR cells are heterogeneous and comprise TH1-like TR cells as well as previously described TH2-like TR cells, which express Foxp3 and are induced during the development of respiratory tolerance by CD8- DCs.
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