The first such study, conducted by Polanczyk et al., demonstrated that treating EAE (experimental autoimmune encephalomyelitis) mice with 17β-estradiol (E2) leads to increased CD4+CD25+ Treg compartment, FoxP3 expression, and expression of PD-1 on Tregs, macrophages, B cells, and dendritic cells. The gene discussed is CD4; the disease is experimental autoimmune encephalomyelitis.