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.
Highlights
Human T-lymphotropic virus type 1 (HTLV-1) is the human retrovirus firstly discovered in 1980 (Poiesz et al 1980)
HTLV-1 infection of CD4+ T cells is associated with expression of several proteins that are characteristic of Treg cells, in particular CD25, FoxP3, and CCR4
Apoptotic oligodendrocytes were frequently in contact with CD8+ T cells, resulting in demyelination. These findings indicate that the immune responses between HTLV1-specific cytotoxic T lymphocytes (CTL) and HTLV-1-infected CD4+ T cells could cause apoptosis in surrounding neural cells
Summary
Human T-lymphotropic virus type 1 (HTLV-1) is the human retrovirus firstly discovered in 1980 (Poiesz et al 1980). HTLV-1-infected T cells and CD8+ cytotoxic T lymphocytes (CTL) against HTLV-1 invade the central nervous system (CNS) and release proinflammatory cytokines and chemokines, resulting in the tissue damage These immune responses are considered to underlie the pathogenesis of HAMTSP. Both HTLV-1 viral regulatory proteins, Tax and HTLV-1 basic leucine zipper factor (HBZ), play critical roles in immune dysregulation in HAM/TSP (Enose-Akahata et al 2017). The HTLV-1 genome has a pX region including six open reading frames: five on the plus-strand and one on the minus-strand Of these six genes, tax, rex, and HBZ play a key role in the infectivity and proliferation of HTLV-1. Epigenetic modifications may regulate the pattern of proviral transcription and mediate inflammation in HAM/TSP patients, and further studies are necessary to clarify the role of these mechanisms in the pathogenesis of HAM/TSP
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