title: Low frequency of CD94/NKG2A+ T lymphocytes in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis, but not in asymptomatic carriers.
abstract: Human natural killer (NK)-cell receptors are expressed by NK cells and some T cells, primarily TCR+CD8+ cytotoxic T lymphocytes (CTLs). Inhibitory NK cell receptors (iNKRs) can down-regulate antigen-mediated T-cell effector functions, including cytotoxic activity and cytokine release. In the present study we demonstrate that CD3+ T cells that bind tetramers of HLA-E and express its ligand, the NK-cell inhibitory receptor CD94/NKG2A, were significantly decreased in frequency in patients with human T-cell lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) but not in asymptomatic HTLV-1 carriers. These cells were either alphabeta or gammadelta T cells. T-cell receptor (TCR) Vbeta-specific reverse transcription-polymerase chain reaction and spectratyping analysis revealed that the TCR repertoire in directly isolated HLA-E tetramer-positive cells from peripheral blood mononuclear cells was skewed in both HTLV-1-infected and healthy individuals. However, oligoclonally or monoclonally expanded levels of TCR Vbetawere more frequently detected within HTLV-1-infected individuals than healthy controls. Importantly, HLA-E tetramer-positive or NKG2A+ T cells from HTLV-1 patients do not express Tax and display different TCR usage from the immunodominant Tax11-19-specific CD8+ T cells, suggesting that they do not encounter HTLV-1-infected cells. The expression of NK cell-associated receptors by clonally expanded CD8+ T cells during chronic viral infection suggests that these receptors play a role in regulating CD8+ T cell-mediated antiviral immune responses and that a decrease of this cell subset results in an increased risk of inflammatory diseases such as HAM/TSP.
authors.affiliation: Department of Immunology, Imperial College London, St Mary's Campus, London, United Kingdom.
authors.forename: Mineki
authors.initials: M
authors.lastname: Saito
authors.forename: Veronique M
authors.initials: VM
authors.lastname: Braud
authors.forename: Peter
authors.initials: P
authors.lastname: Goon
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Hanon
authors.forename: Graham P
authors.initials: GP
authors.lastname: Taylor
authors.forename: Akiko
authors.initials: A
authors.lastname: Saito
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Eiraku
authors.forename: Yuetsu
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Koichiro
authors.initials: K
authors.lastname: Usuku
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Weber
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Osame
authors.forename: Charles R M
authors.initials: CR
authors.lastname: Bangham
mesh_terms: D015703:Antigens, CD / Q000032:analysis*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002353:Carrier State / Q000276:immunology; D002999:Clone Cells / Q000276:immunology; D004279:DNA, Viral / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D016356:Gene Products, tax / Q000032:analysis; D015329:Gene Rearrangement, T-Lymphocyte; D019674:Genes, T-Cell Receptor beta; D006680:HLA Antigens / Q000032:analysis; D015490:HTLV-I Infections / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D015368:Human T-lymphotropic virus 1 / Q000235:genetics; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D007564:Japan; D037181:Lectins, C-Type / Q000032:analysis*; D018655:Lymphocyte Count; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D015493:Paraparesis, Tropical Spastic / Q000276:immunology*; D011533:Proviruses / Q000235:genetics; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D011971:Receptors, Immunologic / Q000032:analysis*; D055607:Receptors, Natural Killer Cell; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D000097625:HLA-E Antigens
chemical_list: D015703:Antigens, CD; D004279:DNA, Viral; D018984:Epitopes, T-Lymphocyte; D016356:Gene Products, tax; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D016056:Immunodominant Epitopes; D037181:Lectins, C-Type; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D000097625:HLA-E Antigens; C527054:KLRC1 protein, human; C497869:KLRD1 protein, human