Stability and function of regulatory T cells expressing the transcription factor T-bet Journal Article


Authors: Levine, A. G.; Medoza, A.; Hemmers, S.; Moltedo, B.; Niec, R. E.; Schizas, M.; Hoyos, B. E.; Putintseva, E. V.; Chaudhry, A.; Dikiy, S.; Fujisawa, S.; Chudakov, D. M.; Treuting, P. M.; Rudensky, A. Y.
Article Title: Stability and function of regulatory T cells expressing the transcription factor T-bet
Abstract: Adaptive immune responses are tailored to different types of pathogens through differentiation of naive CD4 T cells into functionally distinct subsets of effector T cells (T helper 1 (TH 1), TH 2, and TH 17) defined by expression of the key transcription factors T-bet, GATA3, and RORÎ 3t, respectively. Regulatory T (T reg) cells comprise a distinct anti-inflammatory lineage specified by the X-linked transcription factor Foxp3 (refs 2, 3). Paradoxically, some activated T reg cells express the aforementioned effector CD4 T cell transcription factors, which have been suggested to provide T reg cells with enhanced suppressive capacity. Whether expression of these factors in T reg cells - as in effector T cells - is indicative of heterogeneity of functionally discrete and stable differentiation states, or conversely may be readily reversible, is unknown. Here we demonstrate that expression of the TH 1-associated transcription factor T-bet in mouse T reg cells, induced at steady state and following infection, gradually becomes highly stable even under non-permissive conditions. Loss of function or elimination of T-bet-expressing T reg cells - but not of T-bet expression in T reg cells - resulted in severe TH 1 autoimmunity. Conversely, following depletion of T-bet - T reg cells, the remaining T-bet+ cells specifically inhibited TH 1 and CD8 T cell activation consistent with their co-localization with T-bet+ effector T cells. These results suggest that T-bet+ T reg cells have an essential immunosuppressive function and indicate that T reg cell functional heterogeneity is a critical feature of immunological tolerance. © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
Journal Title: Nature
Volume: 546
Issue: 7658
ISSN: 0028-0836
Publisher: Nature Publishing Group  
Date Published: 2017-06-15
Start Page: 421
End Page: 425
Language: English
DOI: 10.1038/nature22360
PROVIDER: scopus
PMCID: PMC5482236
PUBMED: 28607488
DOI/URL:
Notes: Article -- Export Date: 2 August 2017 -- Source: Scopus
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MSK Authors
  1. Beatrice E Hoyos
    23 Hoyos
  2. Alexander Rudensky
    147 Rudensky
  3. Saskia Hemmers
    16 Hemmers
  4. Rachel E Niec
    8 Niec
  5. Stanislav Dikiy
    11 Dikiy
  6. Michail Schizas
    26 Schizas
  7. Andrew Gould Levine
    7 Levine