In both uninfected RMs experimentally depleted of CD4 T cells and human subjects with idiopathic CD4 lymphopenia (ICL), absence of CD4+ T cells alone was associated with severe ILC deficiencies, providing possible mechanisms of ILC loss in lentiviral immunodeficiency infections and identifying novel determinants of ILC homeostasis in health. The gene discussed is CD4; the disease is idiopathic CD4 lymphocytopenia.