J. Immunol. (29 November 2017) doi:10.4049/jimmunol.1701133

Common γ-chain cytokines such as IL-2 and IL-7 promote the proliferation and survival of T cells but can also trigger the restimulation-induced cell death (RICD) of effector memory T cells (TEM cells) to maintain T cell homeostasis. In The Journal of Immunology, Majri et al. show that the signal transducer STAT5B uniquely triggers the apoptosis of TEM cells, but not that of naive or central memory T cells, via RICD. Mice that lack STAT5B accumulate TEM cells. Additionally, a patient with a heterozygous point mutation in STAT5B also exhibited accumulation of CD4+ TEM cells and clinical symptoms of autoimmunity, as did his heterozygous mother. This Q206R substitution in the STAT5B coiled-coil domain yields a dominant-interfering protein in the IL-2–STAT5 signaling pathway that results in a hypomorphic phenotype. The patient’s TEM cells were also resistant to apoptosis after stimulation in vitro. It is unclear how STAT5B protein–protein interactions trigger RICD, and the identity of those interacting proteins is currently unknown.LAD