Yamaguchi et al. [22] reported FR4 is a functionally essential molecule for Tregs and is constitutively highly expressed on nTregs; they also demonstrated that the blockage of FR4 sufficed to deplete CD25+CD4+ nTregs and that the transfer of FR4hi cell-depleted T-cell suspensions induced autoimmune disease in nude mice that had rejected tumors. This evidence concerns the gene CD4 and autoimmune disease.