Immunopathogenesis of HAM/TSP and Radiological Features of Disease Progression

Human T cell lymphotropic virus type 1 (HTLV-1) is an oncogenic retrovirus associated with the development of several human diseases including the progressive neurological disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). While the complete pathogenesis of HAM/TSP is not fully understood, epidemiological, virological, immunological, and clinical studies have elucidated key components of disease development. Widely recognized characteristics of HAM/TSP include high proviral load (PVL) and hyperinflammatory cellular immune responses. Histological studies have demonstrated that proinflammatory immune infiltrates, most notably HTLV-1-specific CD8+ T cells, accumulate within the spinal cord and are associated with tissue degradation and symptom severity. This review will summarize the pathophysiological features of HAM/TSP. Particular attention will be paid to recent advancements in magnetic resonance imaging (MRI) of the central nervous system (CNS) that have expanded our understanding of disease progression, especially changes to the spinal cord. These imaging advances have demonstrated that HAM/TSP is characterized by a disease-specific pattern of spinal cord atrophy that is well correlated with clinical, virological, and immunological parameters of disease development.