CD8 T-Cell Terminal Differentiation and Its Regulation by DHEA in HIV-TB Coinfection

GUADALUPE SUAREZ; MATIAS ANGERAMI; MARIA VECCHIONE; HORACIO SALOMON; MARIA QUIROGA; OMAR SUED

Seattle, Washington

Congreso; CROI 2015; 2015

Conference on Retroviruses and Opportunistic Infections (CROI)

Background: Tuberculosis (TB) is the first cause of death in HIV+ patients. Mtb infection elicits CD8 T cell (CD8Tc) responses that contribute to control latent TB (LTB). We previously showed that Dehydroepiandrosterone (DHEA) in vitro reduces FoxP3 expression while raises Mtb-induced IFN-􀁡 release in HIV-TB patients. In this study we explored the anti-tubercular function and effector/memory phenotype of CD8Tc during HIV-TB co-infection and their modulation by DHEA. Methods: 47 HIV+ with active TB (HIV-TB), 12 HIV+/TST+ (HIV-LTB), 12 HIV+/TST- (HIV+) and 25 healthy (HD) individuals were studied. Memory subsets, determined by CD27 and CD45RA staining, and ex-vivo IFN-􀁡 production and CD107a/b staining in CD8Tc were assessed by flow cytometry. DHEA plasma levels were measured and the expression of transcription factors involved in effector/memory setting was evaluated by RT-PCR. Data was analyzed by using non-parametric tests. Results: Bulk CD8Tc in HIV+, HIV-LTB and HIV-TB patients showed different memory subset distribution compared to HD (p