While DN T cells can be detected at low frequencies in peripheral blood of healthy individuals (Fig. 3 G), they are however expanded and pathognomonic of diseases of immune dysregulation such as autoimmune lymphoproliferative syndrome (ALPS) due to FAS deficiency (Seif et al., 2010), PD-1 deficiency (Ogishi et al., 2021), or STAT3 gain of function (GOF) (Nabhani et al., 2017). Here, PDCD1 is linked to autoimmune lymphoproliferative syndrome.