HIV -TB co -infection impairs CD8+ T cell differentiation and function while dehydroepiandrosterone improves cytotoxic anti -tubercular immune responses

SUAREZ G; ANGERAMI M; VECCHIONE M; LAUFER N; TURK G; RUIZ MJ; MESCH V; FABRE V; MAIDANA P; AMERI D; CAHN P; SUED O; SALOMON H; BOTTASSO O; QUIROGA MF

EUROPEAN JOURNAL OF IMMUNOLOGY

WILEY-V C H VERLAG GMBH

Lugar: Weinheim; Año: 2015 vol. 45 p. 2529 - 2541

0014-2980

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-g 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 naive 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.