Inducible Costimulator (ICOS): a modulator of IFN-g production in human tuberculosis.

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

Boston

Congreso; Annual Meeting of The American Association of Immunologists (AAI); 2006

AAI

Effective host defense against Mycobacterium tuberculosis requires the induction of T helper 1 (Th1) cytokine responses. We investigated the role of ICOS, a receptor known to regulate Th cytokine production in the context of tuberculosis. Patients with active disease, classified as high responder (HR) or low responder (LR) according to their in vitro T cell responses to the antigen, were evaluated for T cell expression of ICOS, T-bet and GATA-3 levels after antigen-stimulation. M. tuberculosis significantly increased ICOS levels in HR patients, up-regulated T-bet and down-regulated GATA-3 levels. In contrast, antigen stimulation didn?t modify ICOS in LR patients, but increased GATA-3 and decreased T-bet levels. Moreover, in HR patients ICOS was up-regulated by Th1 cytokines and downregulated by Th2 cytokines. Furthermore, ICOS ligation augmented M. tuberculosis-induced IFN-γ from responsive individuals. In contrast, neither TH1 or Th2 cytokines dramatically affected ICOS levels on T cells from LR patients, and ICOS activation didn?t enhance IFN-γ. However, simultaneous activation of ICOS and CD3 slightly augmented IFN-γ secretion by LR patients. Together, our data suggest that ICOS activation may promote the induction of protective Th1 cytokine responses to intracellular bacterial pathogens.