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

Wim Pierson, Bénédicte Cauwe, Antonia Policheni, Susan M Schlenner, Dean Franckaert, Julien Berges, Stephanie Humblet-Baron, Susann Schönefeldt, Marco J Herold, David Hildeman, Andreas Strasser, Philippe Bouillet, Li-Fan Lu9, Patrick Matthys0, Antonio A Freitas, Rita J Luther, Casey T Weaver, James Dooley, Daniel H D Gray and Adrian Liston
Nature immunology

Foxp3(+) regulatory T (Treg) cells are a crucial immunosuppressive population of CD4(+) T cells, yet the homeostatic processes and survival programs that maintain the Treg cell pool are poorly understood. Here we report that peripheral Treg 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 Treg cells are removed by attrition, dependent on the Bim-initiated Bak- and Bax-dependent intrinsic apoptotic pathway. The antiapoptotic proteins Bcl-xL and Bcl-2 were dispensable for survival of Treg cells, whereas Mcl-1 was critical for survival of Treg cells, and the loss of this antiapoptotic protein caused fatal autoimmunity. Together, these data define the active processes by which Treg cells maintain homeostasis via critical survival pathways.