title: In vivo expression of human T-lymphotropic virus type 1 basic leucine-zipper protein generates specific CD8+ and CD4+ T-lymphocyte responses that correlate with clinical outcome.
abstract: BACKGROUND
  The roles of the human T-lymphotropic virus type 1 (HTLV-1) basic leucine zipper (HBZ) gene are not clearly understood. We examined CD8+ and CD4+ T cell responses to HBZ and compared these with Tax responses.
  
  
  METHODS
  Interferon (IFN)-γ and interleukin (IL)-2-secreting T cells were detected by enzyme-linked immunosorbent spot (ELISpot) assays of freshly isolated peripheral blood mononuclear cells (PBMCs) stimulated with synthetic HBZ or Tax peptides. Ten patients with HTLV-1-associated myelopathy (HAM) and 20 asymptomatic HTLV-1 carriers (ACs), (10 high, 10 low viral load).
  
  
  RESULTS
  Of 30 study participants, 17 had detectable HBZ-specific CD4+ T cells and 12 had HBZ-specific CD8+ T cell responses. Detection of Tax-specific CD4+ T cells (IL-2- or IFN-γ-secreting) did not differ by disease status, but Tax-specific CD8+ T cell responses were more commonly detected in patients with HAM. HBZ-specific CD4+ or CD8+ T cells were less likely to be detected than Tax-specific T cells. IL-2-secreting Tax-specific CD8+ T cells, and IFN-γ-secreting Tax-specific CD4+ T cells were associated with HAM. Low viral load, asymptomatic HTLV-1 carriage was associated with IL-2-secreting CD8+ T cells specific for HBZ.
  
  
  CONCLUSIONS
  HBZ protein is expressed in vivo in patients with HAM and in ACs. Our results are consistent with the idea that the T cell response to HBZ plays an important part in restricting HTLV-1 viral load.
authors.affiliation: Infectious Diseases, Faculty of Medicine, Imperial College, Norfolk Place, London, England.
authors.forename: Silva
authors.initials: S
authors.lastname: Hilburn
authors.forename: Aileen
authors.initials: A
authors.lastname: Rowan
authors.forename: Maria-Antonietta
authors.initials: MA
authors.lastname: Demontis
authors.forename: Aidan
authors.initials: A
authors.lastname: MacNamara
authors.forename: Becca
authors.initials: B
authors.lastname: Asquith
authors.forename: Charles R M
authors.initials: CR
authors.lastname: Bangham
authors.forename: Graham P
authors.initials: GP
authors.lastname: Taylor
mesh_terms: D050976:Basic-Leucine Zipper Transcription Factors / Q000276:immunology*; D001769:Blood / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D058501:Enzyme-Linked Immunospot Assay; D016356:Gene Products, tax / Q000276:immunology; D015490:HTLV-I Infections / Q000276:immunology* / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D012191:Retroviridae Proteins; D016896:Treatment Outcome; D014764:Viral Proteins / Q000276:immunology*
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D016356:Gene Products, tax; C479751:HBZ protein, human T-cell leukemia virus type I; D007376:Interleukin-2; D012191:Retroviridae Proteins; D014764:Viral Proteins; C514970:tax protein, Human T-lymphotrophic virus 1; D007371:Interferon-gamma