Abundant evidence shows that higher numbers of Tregs prevent or halt many diverse and spontaneous forms of autoimmunity, especially in animal models.1, 2 Tregs are commonly identified as CD4+CD25+Foxp3+ cells, but within peripheral T cells there are two functionally heterogeneous subgroups defined by expression of CD45RA or RO.3, 4 One subgroup is resting Tregs (rTregs, CD4+CD25+Foxp3+CD45RO−RA+) and the other is activated Tregs (aTregs, CD4+CD25+Foxp3+CD45RA-RO+).5 When rTregs are converted to aTregs, they display high expression of tumor necrosis factor (TNF) receptor 2. The gene discussed is CD4; the disease is Autoimmunity.