Mediators of central nervous system damage during the progression of human T-cell leukemia type I-associated myelopathy/tropical spastic paraparesis

Kate Barmack, Edward W. Harhaj, Brian Wigdahl

Research output: Contribution to journalReview article

Abstract

Human T-cell leukemia virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) represents one of the most devastating diseases associated with HTLV-I infection. Despite the delineation of clinical features associated with this neurologic disease, more progress needs to be made with respect to understanding the molecular mechanisms relating to the genesis of HAM/TSP. Several factors have been hypothesized to contribute to whether an HTLV-I-infected individual remains asymptomatic, develops adult T-cell leukemia (ATL), or progresses to HAM/TSP. Among the most intriguing of these factors is the immune response mounted by the host against HTLV-I. Several cell populations are crucial with respect to generating an efficient immune response against the virus. This includes CD4+ T cells, CD8+ T cells, dendritic cells (DCs), monocytes/macrophages, and HTLV-I-infected cells that interact with immune cells to stimulate their effector functions. Although all of these cell types likely play important roles in the etiology of HAM/TSP, this review focuses specifically on the potential function of the CD8+ T-cell population during the progression of HTLV-I-induced neurologic disease. The immune response in HAM/TSP patients may transition from a beneficial response aimed at controlling the viral infection, to a detrimental response that ultimately participates in mediating the pathology observed in HAM/TSP. In this respect, the generation of a hyperactive CD8+ cytotoxic T lymphocyte (CTL) response primarily targeting the HTLV-I Tax protein likely plays a key role in the genesis of pathologic abnormalities associated with HAM/TSP. The efficiency and activity of Tax-specific CD8+ CTLs maybe regulated at a number of levels, and deregulation of Tax-specific CTL activation may contribute to HAM/TSP. This review focuses on potential mechanisms of central nervous system (CNS) damage associated with the genesis of HAM/TSP following HTLV-I infection, focusing on the role of the Tax-specific CTL compartment.

Original languageEnglish (US)
Pages (from-to)522-529
Number of pages8
JournalJournal of neurovirology
Volume9
Issue number5
StatePublished - Oct 1 2003

Keywords

  • Blood-brain barrier
  • CD8 T cells
  • CTLs
  • Cerebrospinal fluid
  • Denritic cells
  • HAM/TSP
  • HTLV-I
  • Molecular mimickry
  • Neurologic disease
  • Retrovirus
  • Tax

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Virology

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