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Human T-lymphotrophic virus type I (HTLV-I) is an oncogenic retrovirus and its infection is associated with a variety of human diseases including HTLV-I-associated myelopathy/tropic spastic paraparesis (HAM/TSP). Large numbers of epidemiological, virological, immunological, and clinical studies on HTLV-I- and HTLV-I-associated diseases have been published, although the pathogenesis of HAM/TSP remains to be fully understood. In the last several years, researchers have shown that several key factors are important in HTLV-I-associated neurologic disease including high HTLV-I proviral load and a strong immune response to HTLV-I. Here, we review pathophysiological findings on HAM/TSP and focus on viral-host immune responses to the virus in HTLV-I infected individuals. In particular, the role of HTLV-I-specific CD8+ T cell response is highlighted.