title: IFN-gamma production in response to Tax 161-233, and frequency of CD4+ Foxp3+ and Lin HLA-DRhigh CD123+ cells, discriminate HAM/TSP patients from asymptomatic HTLV-1-carriers in a Peruvian population.
abstract: Human T-lymphotropic virus 1 (HTLV-1) can cause HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The objective of this study was to gain insight into the pathogenesis of HAM/TSP by focusing on the CD8(+) T-cell response. Twenty-three HTLV-1-seronegative controls (SC), 29 asymptomatic HTLV-1 carriers (AC) and 48 patients with HAM/TSP were enrolled in the study. We evaluated the production of interferon-gamma (IFN-gamma) in peripheral blood mononuclear cells stimulated with Tax overlapping peptides, the expression of genes related to the CD8(+) cytotoxic T-cell response, the frequency of CD4(+) Foxp3(+) cells and of dendritic cells, and the HTLV-1 provirus load (PVL). The frequency of cells producing IFN-gamma in response to Tax 161-233, but not to Tax 11-19, discriminated patients with HAM/TSP from AC. The increased pro-inflammatory response observed in patients with HAM/TSP was shared by AC with a high PVL, who also exhibited lower levels of granzyme H mRNA in unstimulated CD8(+) T cells than AC with a low PVL. Patients with HAM/TSP showed higher frequencies of CD4(+) Foxp3(+) cells and lower frequencies of plasmacytoid dendritic cells (pDC) than AC. Our findings are consistent with a model in which HTLV-1, along with the host genetic background, drives quantitative and qualitative changes in pDC and CD4(+) Foxp3(+) cells that lead to a predominance of inflammatory responses over lytic responses in the CD8(+) T-cell response of individuals predisposed to develop HAM/TSP.
authors.affiliation: Instituto de Medicina Tropical Alexander von Humboldt, Universidad Peruana Cayetano Heredia, Lima, Peru. 05238@upch.edu.pe
authors.forename: Ivan
authors.initials: I
authors.lastname: Best
authors.forename: Giovanni
authors.initials: G
authors.lastname: López
authors.forename: Kristien
authors.initials: K
authors.lastname: Verdonck
authors.forename: Elsa
authors.initials: E
authors.lastname: González
authors.forename: Martín
authors.initials: M
authors.lastname: Tipismana
authors.forename: Eduardo
authors.initials: E
authors.lastname: Gotuzzo
authors.forename: Guido
authors.initials: G
authors.lastname: Vanham
authors.forename: Daniel
authors.initials: D
authors.lastname: Clark
mesh_terms: D000328:Adult; D000368:Aged; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000821:virology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000821:virology; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015870:Gene Expression; D016356:Gene Products, tax / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology; D015368:Human T-lymphotropic virus 1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000097:blood; D053650:Interleukin-3 Receptor alpha Subunit / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015493:Paraparesis, Tropical Spastic / Q000276:immunology*; D010455:Peptides / Q000276:immunology / Q000494:pharmacology; D010568:Peru; D011533:Proviruses / Q000276:immunology; D019562:Viral Load; D017735:Virus Latency / Q000187:drug effects / Q000276:immunology
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D016356:Gene Products, tax; D006684:HLA-DR Antigens; D053650:Interleukin-3 Receptor alpha Subunit; D010455:Peptides; C514970:tax protein, Human T-lymphotrophic virus 1; D007371:Interferon-gamma