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

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.