Role of signal transduction molecules on the regulation of the pattern of cytokines in human tuberculosis.

VIRGINIA PASQUINELLI; M. FLORENCIA QUIROGA; GUSTAVO J. MARTÍNEZ; VERÓNICA E. GARCÍA

Buenos Aires, Argentina.

Simposio; Symposium on Recent Research Advances in tuberculosis and Mycobacteria. II Argentinean Symposium on Tuberculosis. INCO-DEV Concerted Action Upgrade Improved diagnosis, drug resistance detection and control of tuberculosis in Latin America.; 2003

ANLIS “Dr. Carlos G. Malbran”, CONICET. INTA Castelar, Hospital “Dr. Abel Cetrángolo” SENASA.

Production of the Th1 cytokine IFN-g by T cells is considered crucial for immnunity 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 the 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 signalling 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 response 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 o SAP interferes with Th1 responses while SLAM expression contributes to Th1 cytokine responses in tuberculosis. This study further suggests that SAP and SLAM might be focal points for therapeutic modulation of T cell cytokine responses in tuberculosis.