Expression of SLAM associated protein (SAP) interrupts IFN-gamma production in human tuberculosis.

VIRGINIA PASQUINELLI; MARÍA F. QUIROGA; GUSTAVO MARTÍNEZ; LILIANA CASTRO ZORRILLA; ROSA MARÍA MUSELLA; MARÍA MARTA BRACCO; LILIANA BELMONTE; ALEJANDRO MALBRÁN; LEONARDO FAINBOIM; PETER A. SIELING; VERÓNICA E. GARCÍA.

JOURNAL OF IMMUNOLOGY

AMER ASSOC IMMUNOLOGISTS

Año: 2004 vol. 172 p. 1177 - 1185

0022-1767

Production of the Th1 cytokine IFN-g by T cells is considered crucial for immunity against Mycobacterium tuberculosis infection.  We evaluated IFN-g production in tuberculosis in the context of signaling molecules known to regulate Th1 cytokines.  Two populations of patients with active tuberculosis were identified, based on their T cell responses to the bacterium.  High responder (HR) tuberculosis patients displayed significant M. tuberculosis-dependent T cell proliferation and IFN-g production, while low responder (LR) tuberculosis patients displayed weak or no T cell responses to M. tuberculosis.  The expression of the signaling lymphocytic activation molecule (SLAM) associated protein (SAP) on cells from tuberculosis patients was inversely correlated with IFN-g production in those individuals.  Moreover, patients with a non-functional SAP gene displayed immune responses to M. tuberculosis similar to those of HR patients.  In contrast to SAP, T cell expression of SLAM was directly correlated with responsiveness to M. tuberculosis antigen.  Our data suggest that expression of SAP interferes with Th1 responses while SLAM expression contributes to Th1 cytokine responses in tuberculosis.  The study further suggests that SAP and SLAM might be focal points for therapeutic modulation of T cell cytokine responses in tuberculosis.