A substantial fraction of antigen-specific Tregs with features of Foxp3high, CD25high, and demethylation of the TSDR, induces downregulation of Foxp3 transcription, loss of Foxp3 expression, and development of effector and pathogenic T cell characteristics in an experimental autoimmune encephalomyelitis (EAE) model. This evidence concerns the gene FOXP3 and experimental autoimmune encephalomyelitis.