IFN-β 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

Ivan Best, Giovanni López, Kristien Verdonck, Elsa González, Martín Tipismana, Eduardo Gotuzzo, Guido Vanham, Daniel Clark

Resultado de la investigación: Contribución a una revistaArtículorevisión exhaustiva

24 Citas (Scopus)

Resumen

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-β (IFN-β) 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-β 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.

Idioma originalInglés
Páginas (desde-hasta)e777-e786
PublicaciónImmunology
Volumen128
N.º1 PART 2
DOI
EstadoPublicada - sep 2009
Publicado de forma externa

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Profundice en los temas de investigación de 'IFN-β production in response to Tax 161-233, and frequency of CD4 <sup>+</sup> Foxp3<sup>+</sup> and Lin<sup>-</sup> HLA-DR<sup>high</sup> CD123<sup>+</sup> cells, discriminate HAM/TSP patients from asymptomatic HTLV-1-carriers in a Peruvian population'. En conjunto forman una huella única.

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