Foxp3 super(+)CD25 super(+)CD4 super(+) natural regulatory T cells in dominant self-tolerance and autoimmune disease

Naturally arising CD25 super(+)CD4 super(+) regulatory T (Treg) cells, most of which are produced by the normal thymus as a functionally mature T-cell subpopulation, play key roles in the maintenance of immunologic self-tolerance and negative control of a variety of physiological and pathological im...

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Veröffentlicht in:Immunological reviews 2006-08, Vol.212 (1), p.8-27
Hauptverfasser: Sakaguchi, Shimon, Ono, Masahiro, Setoguchi, Ruka, Yagi, Haruhiko, Hori, Shohei, Fehervari, Zoltan, Shimizu, Jun, Takahashi, Takeshi, Nomura, Takashi
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Sprache:eng
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Zusammenfassung:Naturally arising CD25 super(+)CD4 super(+) regulatory T (Treg) cells, most of which are produced by the normal thymus as a functionally mature T-cell subpopulation, play key roles in the maintenance of immunologic self-tolerance and negative control of a variety of physiological and pathological immune responses. Natural Tregs specifically express Foxp3, a transcription factor that plays a critical role in their development and function. Complete depletion of Foxp3-expressing natural Tregs, whether they are CD25 super(+) or CD25 super(-), activates even weak or rare self-reactive T-cell clones, inducing severe and widespread autoimmune-inflammatory diseases. Natural Tregs are highly dependent on exogenously provided interleukin (IL)-2 for their survival in the periphery. In addition to Foxp3 and IL-2-IL-2 receptor, deficiency or functional alteration of other molecules, expressed by T cells or non-T cells, may affect the development-function of Tregs or self-reactive T cells, or both, and consequently tip the peripheral balance between the two populations toward autoimmunity. Elucidation of the molecular and cellular basis of this Treg-mediated active maintenance of self-tolerance will facilitate both our understanding of the pathogenetic mechanism of autoimmune disease and the development of novel methods of autoimmune disease prevention and treatment via enhancing and re-establishing Treg-mediated dominant control over self-reactive T cells.
ISSN:0105-2896
1600-065X
DOI:10.1111/j.0105-2896.2006.00427.x