HIV alters Mycobacterium tuberculosis-induced T cell responses in patients with tuberculosis

QUIROGA MF; PASQUINELLI V; MARTÍNEZ GJ; JURADO JO; MUSELLA RM; CASTRO ZORRILLA L; ABBATE E; SALOMÓN H; GARCÍA VE

Córdoba, Argentina

Congreso; VII Congreso Latinoamericano de Inmunología; 2005

SAI

HIV infection is associated with a generalized defect in cellular mediated immunity.  Since the cytokines produced by T-cells are crucial in the susceptibility to tuberculosis (TB), we investigated whether HIV alters the responses to Mycobacterium tuberculosis (Mtb).  Given that several signaling proteins modulate T-cell cytokine patterns, we analyzed T-cell costimulatory molecules’ expression and cytokine production in HIV+ (HIV-TB ) and HIV- TB patients.  Based on their T cell proliferation, IFN-g production, and SLAM (signaling lymphocytic activation molecule) expression, we found high responder (HR) and low responder (LR) patients. Basal expression (determined by flow cytometry) of SLAM, ICOS (inducible costimulator), PD-1 (programmed death-1) and CTLA-4 in HIV-TB was significantly increased compared to healthy donors, whereas only SLAM were significantly increased in TB patients. Moreover, after Mtb stimulation, two groups of HIV-TB patients were observed: HR (HR-HIV-TB), individuals with increased proliferation index (12,1±7), IFN-g (4455±2810 pg/ml) and IL-10 (1638±360 pg/ml) production, and LR (LR-HIV-TB) that secreted only low levels of IL-10.  Furthermore, SLAM, ICOS, PD-1 and CTLA-4 expression on T cells from HR-HIV-TB, HR-TB and healthy donors increased after Mtb stimulation compared to LR-HIV-TB or LR-TB. Our results suggest that HIV infection might modify the expression and function of costimulatory molecules, contributing to induce different Th cytokine profiles in HIV-TB.