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Although the structure of human T lymphoptropic virus type I (HTLV-I) has been known well, the function of some proteins encoded by HTLV-I PX region is not fully understood. Furthermore, the responses of the immune system to HTLV-I remain still unknown. Most of HTLV-I-infected individuals show a strong and persistently activated cytotoxic T-cell (CTL) response to the virus. The frequency of HTLV-I specific CTL is higher in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) compared with HTLV-I carriers. However, the efficacy of the immune response determines the outcome of HTLV-I-associated diseases. Among the risk factors which contribute to the observed differences between HAM/TSP patients and HTLV-I carriers, the interaction between different genes and/or environmental factors seem to be important. These factors may also involve in outcome of HTLV-I infection in infected-individuals.