Antiapoptotic McI-1 is critical for the survival and niche-filling capacity of Foxp3+ regulatory T cells

Academic Article

Abstract

  • Foxp3+ regulatory T (T reg) cells are a crucial immunosuppressive population of CD4+ T cells, yet the homeostatic processes and survival programs that maintain the T reg cell pool are poorly understood. Here we report that peripheral T reg cells markedly alter their proliferative and apoptotic rates to rapidly restore numerical deficit through an interleukin 2-dependent and costimulation-dependent process. By contrast, excess T reg cells are removed by attrition, dependent on the Bim-initiated Bak-and Bax-dependent intrinsic apoptotic pathway. The antiapoptotic proteins Bcl-x L and Bcl-2 were dispensable for survival of T reg cells, whereas Mcl-1 was critical for survival of T reg cells, and the loss of this antiapoptotic protein caused fatal autoimmunity. Together, these data define the active processes by which T reg cells maintain homeostasis via critical survival pathways. ¬© 2013 Nature America, Inc. All rights reserved.
  • Digital Object Identifier (doi)

    Pubmed Id

  • 3787282
  • Author List

  • Pierson W; Cauwe B; Policheni A; Schlenner SM; Franckaert D; Berges J; Humblet-Baron S; Sch√∂nefeldt S; Herold MJ; Hildeman D
  • Start Page

  • 959
  • End Page

  • 965
  • Volume

  • 14
  • Issue

  • 9