The p53 effector Perp mediates the persistence of CD4⁺ effector memory T-cell undergoing lymphopenia-induced...

Under lymphopenic conditions, the rapid spontaneous proliferation produces cells that robustly differentiate into effector memory T (T_EM) cells, and the aberrant expansion is preferentially driven by self-antigens. The pool size of effector memory T-cell is governed by a complex homeostatic balance between proliferation and death. Perp is a critical effector involved in the p53-dependent apoptotic pathway and widely expressed in mammalian tissues. We have previously shown that Perp has a prominent role in activation-induced cell death of peripheral Th17 cells. Here, we show that Peripheral Perp^-/-CD4⁺ T_EM cells outcompete wild type T_EM cells for access to splenic niches in vivo. The skewing of the Perp^-/- T_EM cells compartment was not the result of a difference in lymphopenia-induced proliferation, but the resistance to apoptosis, particularly after anti-Fas treatment. Data presented in this work indicate that Perp mediates the persistence of CD4⁺ T_EM cells in irradiation-induced lymphopenic settings.