Induction of T helper type 1-like regulatory cells that express Foxp3 and protect against airway hyper-reactivity

Nat Immunol. 2004 Nov;5(11):1149-56. doi: 10.1038/ni1122. Epub 2004 Sep 26.


The range of regulatory T cell (T(R) cell) types that control immune responses is poorly understood. We describe here a population of T(R) cells that developed in vivo from naive CD4(+)CD25(-) T cells during a T helper type 1 (T(H)1)-polarized response, distinct from CD25(+) T(R) cells. These antigen-specific T(R) cells were induced by CD8alpha(+) DCs, produced both interleukin 10 and interferon-gamma, and potently inhibited the development of airway hyper-reactivity. These T(R) cells expressed the transcription factors Foxp3 and T-bet, indicating that these T(R) cells are related to T(H)1 cells. Thus, adaptive T(R) cells are heterogeneous and comprise T(H)1-like T(R) cells as well as previously described T(H)2-like T(R) cells, which express Foxp3 and are induced during the development of respiratory tolerance by CD8alpha(-) DCs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Differentiation, T-Lymphocyte / metabolism
  • CD8 Antigens / immunology
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / immunology
  • DNA-Binding Proteins / metabolism
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Forkhead Transcription Factors
  • Inducible T-Cell Co-Stimulator Protein
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Mice
  • Respiratory System / immunology*
  • T-Box Domain Proteins
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Transcription Factors / metabolism


  • Antigens, Differentiation, T-Lymphocyte
  • CD8 Antigens
  • CD8alpha antigen
  • DNA-Binding Proteins
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Icos protein, mouse
  • Inducible T-Cell Co-Stimulator Protein
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Transcription Factors
  • Interleukin-10
  • Interferon-gamma