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

• Autores: Best, I, Lopez, G, Verdonck, K, Gonzalez, E, Tipismana, M, Gotuzzo, E, Vanham, G, Clark, D
• Formato: artículo
• Fecha de Publicación: 2009
• Institución: Consejo Nacional de Ciencia Tecnología e Innovación
• Repositorio: CONCYTEC-Institucional
• Lenguaje: inglés
• OAI Identifier: oai:repositorio.concytec.gob.pe:20.500.12390/1157
• Enlace del recurso: https://hdl.handle.net/20.500.12390/1157; https://doi.org/10.1111/j.1365-2567.2009.03082.x
• Nivel de acceso: acceso abierto
• Materia: CD8+ T-cell response; Human T-lymphotropic virus 1; Paraparesis

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.