title: Increased expression of human T lymphocyte virus type I (HTLV-I) Tax11-19 peptide-human histocompatibility leukocyte antigen A*201 complexes on CD4+ CD25+ T Cells detected by peptide-specific, major histocompatibility complex-restricted antibodies in patients with HTLV-I-associated neurologic disease.
abstract: Human T lymphocyte virus type I (HTLV-I)-associated chronic inflammatory neurological disease (HTLV-I-associated myelopathy/tropical spastic paraparesis [HAM/TSP]) is suggested to be an immunopathologically mediated disorder characterized by large numbers of HTLV-I Tax-specific CD8+ T cells. The frequency of these cells in the peripheral blood and cerebrospinal fluid is proportional to the amount of HTLV-I proviral load and the levels of HTLV-I tax mRNA expression. As the stimulus for these virus-specific T cells are immunodominant peptide-human histocompatibility leukocyte antigen (HLA) complexes expressed on antigen-presenting cells, it was of interest to determine which cells express these complexes and at what frequency. However, until now, it has not been possible to identify and/or quantify these peptide-HLA complexes. Using a recently developed antibody that specifically recognizes Tax11-19 peptide-HLA-A*201 complexes, the level of Tax11-19-HLA-A*201 expression on T cells was demonstrated to be increased in HAM/TSP and correlated with HTLV-I proviral DNA load, HTLV-I tax mRNA load, and HTLV-I Tax-specific CD8+ T cell frequencies. Furthermore, CD4+ CD25+ T cells were demonstrated to be the major reservoir of HTLV-I provirus as well as Tax11-19 peptide-HLA-A*201 complexes. These results indicate that the increased detection and visualization of peptide-HLA complexes in HAM/TSP CD4+ CD25+ T cell subsets that are shown to stimulate and expand HTLV-I Tax-specific CD8+ T cells may play an important role in the pathogenesis of HTLV-I-associated neurological disease.
authors.affiliation: Viral Immunology Section, Neuroimmunology Branch, National Institutes of Health, National Institute of Neurological Disorders and Strokes, Building 10, Room 5B-16, Bethesda, MD 20892, USA.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Yamano
authors.forename: Cyril J
authors.initials: CJ
authors.lastname: Cohen
authors.forename: Norihiro
authors.initials: N
authors.lastname: Takenouchi
authors.forename: Karen
authors.initials: K
authors.lastname: Yao
authors.forename: Utano
authors.initials: U
authors.lastname: Tomaru
authors.forename: Hong-Chuan
authors.initials: HC
authors.lastname: Li
authors.forename: Yoram
authors.initials: Y
authors.lastname: Reiter
authors.forename: Steven
authors.initials: S
authors.lastname: Jacobson
mesh_terms: D015703:Antigens, CD / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D002460:Cell Line; D005434:Flow Cytometry; D016356:Gene Products, tax / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology*; D015490:HTLV-I Infections / Q000276:immunology*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008285:Major Histocompatibility Complex; D009422:Nervous System Diseases / Q000276:immunology* / Q000821:virology; D010446:Peptide Fragments / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D015704:CD4 Antigens; D016356:Gene Products, tax; D015234:HLA-A Antigens; D010446:Peptide Fragments; D015375:Receptors, Interleukin-2