CD4 and tropical spastic paraparesis: However, Tax protein downregulates forkhead box P3 (FoxP3) in CD4+CD25+ T cells due to decreased demethylation of the Foxp3 gene, which caused the decreased suppressive capacity of CD4+CD25+ T cells and stimulation of HTLV-1 Tax-specific CD8+ T cells in HAM/TSP patients [64, 67, 68].