Induced CD4+Foxp3+ regulatory T cells in immune tolerance

Annu Rev Immunol. 2012:30:733-58. doi: 10.1146/annurev-immunol-020711-075043. Epub 2012 Jan 6.


Regulatory T lymphocytes are essential to maintain homeostasis of the immune system, limiting the magnitude of effector responses and allowing the establishment of immunological tolerance. Two main types of regulatory T cells have been identified--natural and induced (or adaptive)-and both play significant roles in tuning down effector immune responses. Adaptive CD4(+)Foxp3(+) regulatory T (iTreg) cells develop outside the thymus under a variety of conditions. These include not only antigen presentation under subimmunogenic or noninflammatory conditions, but also chronic inflammation and infections. We speculate that the different origin of iTreg cells (noninflammatory versus inflammatory) results in distinct properties, including their stability. iTreg cells are also generated during homeostasis of the gut and in cancer, although some cancers also favor expansion of natural regulatory T (nTreg) cells. Here we review how iTreg cells develop and how they participate in immunological tolerance, contrasting, when possible, iTreg cells with nTreg cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • CD4 Antigens / metabolism
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Immune Tolerance / immunology*
  • Lymphoid Tissue / immunology
  • Lymphoid Tissue / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism


  • CD4 Antigens
  • FOXP3 protein, human
  • Forkhead Transcription Factors