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HIV–TB coinfection impairs CD8 + T‐cell differentiation and function while dehydroepiandrosterone improves cytotoxic antitubercular immune responses

2015; Wiley; Volume: 45; Issue: 9 Linguagem: Inglês

10.1002/eji.201545545

1521-4141

Guadalupe Suárez, Matías Tomás Angerami, María Belén Vecchione, Natalia Laufer, Gabriela Turk, María Julia Ruiz, Viviana Mesch, Bibiana Fabre, Patricia Maidana, Diego Ameri, Pedro Cahn, Omar Sued, Horacio Salomón, Óscar Bottasso, María Florencia Quiroga,

HIV Research and Treatment

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 ) CD45RA(dim) 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.