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Immune responses involve mobilization of T cells within naïve and memory compartments. Tightly regulated Ca 2+ levels are essential for balanced immune outcomes. How Ca 2+ contributes to regulating compartment stoichiometry is unknown. Here, we show that plasma membrane Ca 2+ ATPase 4 (PMCA4) is differentially expressed in human CD4 + T compartments yielding distinct store operated Ca 2+ entry (SOCE) profiles. Modulation of PMCA4 yielded a more prominent increase of SOCE in memory than in naïvedoi:10.3389/fimmu.2021.687242.s004 fatcat:bf6vgg5p6rhjjakjrf5mhnumte