In addition, the majority of APDS patients show a progressive CD4+ T cell lymphopenia with a decreased frequency of CD4+ naïve T cells [in contrast to the lethal CD4+ T cell hyperplasia that is described in mice with a T cell-specific deletion of PTEN (71)], but an excessive accumulation of terminally differentiated, senescent CD8+ effector T cells (64). Here, CD4 is linked to activated PI3K-delta syndrome.