Contracting the ‘mus cells’– does down‐sizing suit us for diving into the memory pool?

Summary:  Maintenance of T‐cell homeostasis is critical for normal functioning of the immune system. After thymocyte selection, T cells enter the peripheral lymphoid organs, where they are maintained as naive cells. Transient disruption of homeostasis occurs when naive T cells undergo antigen‐driven expansion and acquire effector functions. Effector T cells then either undergo apoptosis (i.e. contraction at the population level) or survive to become memory cells. This apoptotic process is crucial: it resets T‐cell homeostasis, promotes protective immunity, and limits autoimmunity. Although initial studies using in vitro models supported a role for death receptor signaling, more recent in vivo studies have implicated Bcl‐2 family members as being critical for the culling of T‐cell responses. While several Bcl‐2 family members likely contribute to T‐cell contraction, the pro‐apoptotic molecule Bim and its anti‐apoptotic antagonist Bcl‐2 are essential regulators of the process. This review discusses the progress made in our understanding of the mechanisms underlying contraction of T‐cell responses and how some cells avoid this cell death and become memory T cells.