Protein phosphatase 2A B55ß limits CD8 T cell lifespan following cytokine withdrawal.

How T cells integrate environmental cues into signals that limit the magnitude and length of immune responses is poorly understood. Here, we provide data that demonstrates that B55s, a regulatory subunit of the phosphatase PP2A, represents a molecular link between cytokine concentration and apoptosis in activated CD8 T cells. Through the modulation of AKT, B55s induced the expression of the pro-apoptotic molecule Hrk in response to cytokine withdrawal. Accordingly, B55s and Hrk were both required for in vivo and in vitro contraction of activated CD8 lymphocytes. We show that this process plays a role during clonal contraction, establishment of immune memory, and preservation of peripheral tolerance. This regulatory pathway may represent an unexplored opportunity to end unwanted immune responses, or to promote immune memory.