Artículo
HIV–TB coinfection impairs CD8+ T‐cell differentiation and function while dehydroepiandrosterone improves cytotoxic antitubercular immune responses
Suárez, Guadalupe Verónica
; Angerami, Matias
; Vecchione, María Belén
; Laufer, Natalia Lorna
; Turk, Gabriela Julia Ana
; Ruiz, Maria Julia
; Mesch, Viviana Rosa; Fabre, Bibiana; Maidana, Patricia Nieves Amelia; Ameri, Diego; Cahn, Pedro; Sued, Omar Gustavo; Salomon, Horacio Eduardo
; Bottasso, Oscar Adelmo
; Quiroga, María Florencia
Fecha de publicación:
06/2015
Editorial:
Wiley VCH Verlag
Revista:
European Journal of Immunology
ISSN:
0014-2980
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Tuberculosis (TB) is the leading cause of death among HIV-positive patients. The decreasing frequencies of terminal effector (TTE ) CD8+ T cells may increase reactivation risk in persons latently infected with Mycobacterium tuberculosis (Mtb). We have previously shown that dehydroepiandrosterone (DHEA) increases the protective antitubercular immune responses in HIV-TB patients. Here, we aimed to study Mtb-specific cytotoxicity, IFN-γ secretion, memory status of CD8+ T cells, and their modulation by DHEA during HIV-TB coinfection. CD8+ T cells from HIV-TB patients showed a more differentiated phenotype with diminished naïve and higher effector memory and TTE T-cell frequencies compared to healthy donors both in total and Mtb-specific CD8+ T cells. Notably, CD8+ T cells from HIV-TB patients displayed higher Terminal Effector (TTE ) CD45RAdim proportions with lower CD45RA expression levels, suggesting a not fully differentiated phenotype. Also, PD-1 expression levels on CD8+ T cells from HIV-TB patients increased although restricted to the CD27+ population. Interestingly, DHEA plasma levels positively correlated with TTE in CD8+ T cells and in vitro DHEA treatment enhanced Mtb-specific cytotoxic responses and terminal differentiation in CD8+ T cells from HIV-TB patients. Our data suggest that HIV-TB coinfection promotes a deficient CD8+ T-cell differentiation, whereas DHEA may contribute to improving antitubercular immunity by enhancing CD8+ T-cell functions during HIV-TB coinfection.
Palabras clave:
Coinfection
,
Cd8+ T Cells
,
Cell Differentiation
,
Dhea
,
Hiv
,
Tuberculosis
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(INBIRS)
Articulos de INSTITUTO DE INVESTIGACIONES BIOMEDICAS EN RETROVIRUS Y SIDA
Articulos de INSTITUTO DE INVESTIGACIONES BIOMEDICAS EN RETROVIRUS Y SIDA
Citación
Suárez, Guadalupe Verónica; Angerami, Matias; Vecchione, María Belén; Laufer, Natalia Lorna; Turk, Gabriela Julia Ana; et al.; HIV–TB coinfection impairs CD8+ T‐cell differentiation and function while dehydroepiandrosterone improves cytotoxic antitubercular immune responses; Wiley VCH Verlag; European Journal of Immunology; 45; 9; 6-2015; 2529-2541
Compartir
Altmétricas