info:eu-repo/semantics/article
HIV-TB co-infection impairs CD8+ T-cell differentiation and function while dehydroepiandrosterone improves cytotoxic anti-tubercular immune responses
Fecha
2015-06Registro en:
Suárez, Guadalupe Verónica; Angerami, Matias; Vecchione, María Belén; Laufer, Natalia Lorna; Turk, Gabriela Julia Ana; et al.; HIV-TB co-infection impairs CD8+ T-cell differentiation and function while dehydroepiandrosterone improves cytotoxic anti-tubercular immune responses; Wiley Vch Verlag; European Journal Of Immunology; 45; 9; 6-2015; 2529-2541
0014-2980
Autor
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
Ameri, Diego
Cahn, Pedro
Sued, Omar Gustavo
Salomon, Horacio Eduardo
Bottasso, Oscar Adelmo
Quiroga, María Florencia
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 anti-tubercular 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 (TN) and higher effector memory (TEM) and terminal effector (TTE) T-cell frequencies compared to healthy donors (HD) both in total and Mtb-specific CD8+T cells. Notably, CD8+T cells from HIV-TB patients displayed higher 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. Our data suggest that HIV-TB co-infection promotes a deficient CD8+ T-cell differentiation, whereas DHEA may contribute to improving anti-tubercular immunity by enhancing CD8+T-cell functions during HIV-TB co-infection