Therefore, we hypothesized that persistent T cell activation in patients with HAM/TSP triggered by viral antigens such as HTLV-1 tax together with the downregulation of Foxp3 may result in decline of the CD4+CD25+CCR4+Foxp3+ Treg population and accumulation of Foxp3-negative CD4+CD25+CCR4+ T cells that lack suppressive function, but are capable of exacerbating the disease process. Here, FOXP3 is linked to tropical spastic paraparesis.