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Title
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IFN- production in response to Tax 161233, and frequency of and cells, discriminate HAM/TSP patients from asymptomatic HTLV-1-carriers in a Peruvian population
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Author
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Abstract
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| 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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Language
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English
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Source (journal)
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Immunology / British Society for Immunology. - Oxford, 1958, currens
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Publication
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Oxford
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2009
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ISSN
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0019-2805
[print]
1365-2567
[online]
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Volume/pages
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28
:1:2
(2009)
, p. e777-e786
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ISI
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000268703800063
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Full text (Publisher's DOI)
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