title: HIV-TB coinfection impairs CD8(+) T-cell differentiation and function while dehydroepiandrosterone improves cytotoxic antitubercular immune responses.
abstract: 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.
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA, Universidad de Buenos Aires - CONICET, Argentina.
authors.forename: Guadalupe V
authors.initials: GV
authors.lastname: Suarez
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA, Universidad de Buenos Aires - CONICET, Argentina.
authors.forename: Matías T
authors.initials: MT
authors.lastname: Angerami
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA, Universidad de Buenos Aires - CONICET, Argentina.
authors.forename: María B
authors.initials: MB
authors.lastname: Vecchione
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA, Universidad de Buenos Aires - CONICET, Argentina.|Hospital Juan A. Fernández, Buenos Aires, Argentina.
authors.forename: Natalia
authors.initials: N
authors.lastname: Laufer
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA, Universidad de Buenos Aires - CONICET, Argentina.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Turk
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA, Universidad de Buenos Aires - CONICET, Argentina.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Ruiz
authors.affiliation: Departamento de Bioquímica Clínica, INFIBIOC, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
authors.forename: Viviana
authors.initials: V
authors.lastname: Mesch
authors.affiliation: Departamento de Bioquímica Clínica, INFIBIOC, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
authors.forename: Bibiana
authors.initials: B
authors.lastname: Fabre
authors.affiliation: Departamento de Bioquímica Clínica, INFIBIOC, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
authors.forename: Patricia
authors.initials: P
authors.lastname: Maidana
authors.affiliation: Hospital Juan A. Fernández, Buenos Aires, Argentina.
authors.forename: Diego
authors.initials: D
authors.lastname: Ameri
authors.affiliation: Hospital Juan A. Fernández, Buenos Aires, Argentina.|Área de Investigaciones Médicas, Fundación Huésped, Buenos Aires, Argentina.
authors.forename: Pedro
authors.initials: P
authors.lastname: Cahn
authors.affiliation: Área de Investigaciones Médicas, Fundación Huésped, Buenos Aires, Argentina.
authors.forename: Omar
authors.initials: O
authors.lastname: Sued
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA, Universidad de Buenos Aires - CONICET, Argentina.
authors.forename: Horacio
authors.initials: H
authors.lastname: Salomón
authors.affiliation: Instituto de Inmunología Clínica y Experimental de Rosario (IDICER), CONICET-UNR, Rosario, Santa Fe, Argentina.
authors.forename: Oscar A
authors.initials: OA
authors.lastname: Bottasso
authors.affiliation: Instituto de Investigaciones Biomédicas en Retrovirus y SIDA, Universidad de Buenos Aires - CONICET, Argentina.
authors.forename: María F
authors.initials: MF
authors.lastname: Quiroga
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000382:microbiology / Q000821:virology; D002454:Cell Differentiation / Q000187:drug effects; D060085:Coinfection; D003430:Cross-Sectional Studies; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D015497:HIV-1 / Q000276:immunology; D054884:Host-Pathogen Interactions; D006801:Humans; D055985:Latent Tuberculosis / Q000276:immunology* / Q000382:microbiology / Q000821:virology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology; D061251:Primary Cell Culture; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology / Q000821:virology; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000382:microbiology / Q000821:virology
chemical_list: D003687:Dehydroepiandrosterone
keywords: CD8+ T cells; Cell differentiation; Coinfection; DHEA; HIV; Tuberculosis