HIV modifies T-cell responses against Mycobacterium tuberculosis in patients with tuberculosis.

F. QUIROGA; V. PASQUINELLI; G. MARTÍNEZ; , J. JURADO; R. MUSELLA; L. CASTRO ZORRILLA; E. ABBATE; H. SALOMÓN,; V. GARCÍA

Córdoba, Argentina

Congreso; VII Congreso Latinoamericano de Inmunología, ALAI 2005; 2005

ALAI

HIV modifies T-cell responses against Mycobacterium tuberculosis in patients with tuberculosis. Quiroga MF1,2, Pasquinelli V1,2, Martinez GJ1,2, Jurado J1,2, Musella R3, Castro Zorrilla L4, Abbate E3,4, Salomon H1, and Garcia VE1. 1Department of Microbiology, 2Division of Immunogenetics, UBA School of Medicine; 3Hospital Muñiz; 4Instituto Vaccarezza UBA. 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.