Natural and adaptive foxp3+ regulatory T cells: more of the same or a division of labor?

Immunity. 2009 May;30(5):626-35. doi: 10.1016/j.immuni.2009.05.002.


Adaptive Foxp3(+)CD4(+) regulatory T (iTreg) cells develop outside the thymus under subimmunogenic antigen presentation, during chronic inflammation, and during normal homeostasis of the gut. iTreg cells are essential in mucosal immune tolerance and in the control of severe chronic allergic inflammation, and most likely are one of the main barriers to the eradication of tumors. The Foxp3(+) iTreg cell repertoire is drawn from naive conventional CD4(+) T cells, whereas natural Treg (nTreg) cells are selected by high-avidity interactions in the thymus. The full extent of differences and similarities between iTreg and nTreg cells is yet to be defined. We speculate that iTreg cell development is driven by the need to maintain a noninflammatory environment in the gut, to suppress immune responses to environmental and food allergens, and to decrease chronic inflammation, whereas nTreg cells prevent autoimmunity and raise the activation threshold for all immune responses.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Differentiation / immunology*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Forkhead Transcription Factors / immunology*
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Immune Tolerance / immunology
  • Infections / immunology
  • Inflammation / immunology
  • Interleukin-15 / immunology
  • Interleukin-15 / metabolism
  • Interleukin-2 / immunology
  • Interleukin-2 / metabolism
  • Neoplasms / immunology
  • STAT Transcription Factors / immunology
  • STAT Transcription Factors / metabolism
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • Thymus Gland / immunology
  • Thymus Gland / metabolism
  • Transforming Growth Factor beta / immunology
  • Transforming Growth Factor beta / metabolism
  • Tretinoin / immunology
  • Tretinoin / metabolism


  • Forkhead Transcription Factors
  • Interleukin-15
  • Interleukin-2
  • STAT Transcription Factors
  • Transforming Growth Factor beta
  • Tretinoin