Human T-lymphotropic virus type 1 (HTLV-1) and cellular immune response in HTLV-1-associated myelopathy/tropical spastic
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REVIEW
Human T-lymphotropic virus type 1 (HTLV-1) and cellular immune response in HTLV-1-associated myelopathy/tropical spastic paraparesis Satoshi Nozuma 1 & Ryuji Kubota 2 & Steven Jacobson 1 Received: 29 March 2020 / Revised: 29 March 2020 / Accepted: 6 July 2020 # The Author(s) 2020
Abstract Human T-lymphotropic virus type 1 (HTLV-1) is associated with adult T cell leukemia/lymphoma and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP is an inflammatory disease of the spinal cord and clinically characterized by progressive spastic paraparesis, urinary incontinence, and mild sensory disturbance. The interaction between the host immune response and HTLV-1-infected cells regulates the development of HAM/TSP. HTLV-1 preferentially infects CD4+ T cells and is maintained by proliferation of the infected T cells. HTLV-1-infected cells rarely express viral antigens in vivo; however, they easily express the antigens after short-term culture. Therefore, such virus-expressing cells may lead to activation and expansion of antigen-specific T cell responses. Infected T cells with HTLV-1 and HTLV-1-specific CD8+ cytotoxic T lymphocytes invade the central nervous system and produce various proinflammatory cytokines and chemokines, leading to neuronal damage and degeneration. Therefore, cellular immune responses to HTLV-1 have been considered to play important roles in disease development of HAM/TSP. Recent studies have clarified the viral strategy for persistence in the host through genetic and epigenetic changes by HTLV-1 and host immune responses including T cell function and differentiation. Newly developed animal models could provide the opportunity to uncover the precise pathogenesis and development of clinically effective treatment. Several molecular target drugs are undergoing clinical trials with promising efficacy. In this review, we summarize recent advances in the immunopathogenesis of HAM/TSP and discuss the perspectives of the research on this disease. Keywords HTLV-1 . HAM/TSP . Neurological disorders . Immunology . Pathogenesis
Introduction Human T-lymphotropic virus type 1 (HTLV-1) is the human retrovirus firstly discovered in 1980 (Poiesz et al. 1980). The main highly endemic areas are the Southwestern part of Japan, the Caribbean, South America, Central and Southern Africa, Middle East, and Central Australia. It is estimated that at least five to ten million people are infected with HTLV-1, but the current number of HTLV-1 carries might be much higher due to a lack of systematic epidemiological studies in most * Steven Jacobson [email protected] 1
Viral Immunology Section, Division of Neuroimmunology and Neurovirology, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
2
Division of Neuroimmunology, Joint Research Center for Human Retrovirus Infection, Kagoshima University, Kagoshima, Japan
endemic regions (Gessain and Cassar 2012). For example, it recently reported that more than 40% of central Australian Indigeno
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