Title
IFN-<tex>$\gamma$</tex> production in response to Tax 161233, and frequency of <tex>$CD4^{+}$</tex> <tex>$Foxp3^{+}$</tex> and <tex>$Lin^{-}$</tex> <tex>$HLA-DR^{high}$</tex> <tex>$CD123^{+}$</tex> cells, discriminate HAM/TSP patients from asymptomatic HTLV-1-carriers in a Peruvian population IFN-<tex>$\gamma$</tex> production in response to Tax 161233, and frequency of <tex>$CD4^{+}$</tex> <tex>$Foxp3^{+}$</tex> and <tex>$Lin^{-}$</tex> <tex>$HLA-DR^{high}$</tex> <tex>$CD123^{+}$</tex> cells, discriminate HAM/TSP patients from asymptomatic HTLV-1-carriers in a Peruvian population
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Publication type
article
Publication
Oxford ,
Subject
Human medicine
Source (journal)
Immunology / British Society for Immunology. - Oxford, 1958, currens
Volume/pages
28(2009) :1:2 , p. e777-e786
ISSN
0019-2805
1365-2567
ISI
000268703800063
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
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-ã (IFN-ã) 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-ã in response to Tax 161233, but not to Tax 1119, 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.
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