title: Human T cell lymphotropic virus type I (HTLV-I)-specific CD4+ T cells: immunodominance hierarchy and preferential infection with HTLV-I.
abstract: CD4(+) T cells predominate in early lesions in the CNS in the inflammatory disease human lymphotropic T cell virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP), but the pathogenesis of the disease remains unclear and the HTLV-I-specific CD4(+) T cell response has been little studied. We quantified the IFN-gamma-producing HTLV-I-specific CD4(+) T cells, in patients with HAM/TSP and in asymptomatic carriers with high proviral load, to test two hypotheses: that HAM/TSP patients and asymptomatic HTLV-I carriers with a similar proviral load differ in the immunodominance hierarchy or the total frequency of specific CD4(+) T cells, and that HTLV-I-specific CD4(+) T cells are preferentially infected with HTLV-I. The strongest CD4(+) T cell response in both HAM/TSP patients and asymptomatic carriers was specific to Env. This contrasts with the immunodominance of Tax in the HTLV-I-specific CD8(+) T cell response. The median frequency of HTLV-I-specific IFN-gamma(+) CD4(+) T cells was 25-fold greater in patients with HAM/TSP (p = 0.0023, Mann-Whitney) than in asymptomatic HTLV-I carriers with a similar proviral load. Furthermore, the frequency of CD4(+) T cells infected with HTLV-I (expressing Tax protein) was significantly greater (p = 0.0152, Mann-Whitney) among HTLV-I-specific cells than CMV-specific cells. These data were confirmed by quantitative PCR for HTLV-I DNA. We conclude that the high frequency of specific CD4(+) T cells was associated with the disease HAM/TSP, and did not simply reflect the higher proviral load that is usually found in HAM/TSP patients. Finally, we conclude that HTLV-I-specific CD4(+) T cells are preferentially infected with HTLV-I.
authors.affiliation: Department of Immunology, Imperial College London, London, United Kingdom.
authors.forename: Peter K C
authors.initials: PK
authors.lastname: Goon
authors.forename: Tadahiko
authors.initials: T
authors.lastname: Igakura
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Hanon
authors.forename: Angelina J
authors.initials: AJ
authors.lastname: Mosley
authors.forename: Anna
authors.initials: A
authors.lastname: Barfield
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Barnard
authors.forename: Lambrini
authors.initials: L
authors.lastname: Kaftantzi
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Graham P
authors.initials: GP
authors.lastname: Taylor
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Weber
authors.forename: Charles R M
authors.initials: CR
authors.lastname: Bangham
mesh_terms: D000595:Amino Acid Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002353:Carrier State / Q000276:immunology / Q000473:pathology / Q000821:virology; D003587:Cytomegalovirus / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D015686:Gene Products, env / Q000276:immunology; D016356:Gene Products, tax / Q000276:immunology; D015490:HTLV-I Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D018655:Lymphocyte Count; D008969:Molecular Sequence Data; D015493:Paraparesis, Tropical Spastic / Q000276:immunology / Q000473:pathology / Q000821:virology; D011533:Proviruses / Q000276:immunology; D019562:Viral Load
chemical_list: D018984:Epitopes, T-Lymphocyte; D015686:Gene Products, env; D016356:Gene Products, tax; D016056:Immunodominant Epitopes