Helios deficiency, either in mice lacking Helios in all cells [38] or specifically in FoxP3+ cells [63] (mostly CD4+ Tregs), leads to an autoimmune phenotype at 5–6 months of age that is associated with distinct symptoms, reproducing some canonical immunological manifestations of lupus: hypergammaglobulinemia against nuclear antigens, splenomegaly, glomerulonephritis, an enhanced presence of activated Tconvs, and an expansion of follicular T lymphocytes (see below). This evidence concerns the gene IKZF2 and Splenomegaly.