ALPS was first described in the 1990s in a cohort of patients with chronic lymphoproliferation and an increased number of double negative T cell populations (DNTs; cell phenotype CD4−/CD8−, CD3+, TCRαβ+), which reach <1% in the peripheral blood of healthy controls (vs. >2.5% in ALPS patients) [85]. Here, CD4 is linked to autoimmune lymphoproliferative syndrome.