ICOS (INDUCIBLE COSTIMULATOR) MODULATES CYTOKINE RESPONSES IN HUMAN TUBERCULOSIS.

G. MARTÍNEZ; V. PASQUINELLI; F. QUIROGA; J. JURADO; R. MUSELLA; L. CASTRO ZORRILLA; M. BALDINI; E . ABBATE; V. GARCÍA

Córdoba, Argentina

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

ALAI

ICOS (INDUCIBLE COSTIMULATOR) MODULATES CYTOKINE RESPONSES IN HUMAN TUBERCULOSIS. MARTINEZ G1, PASQUINELLI V1, QUIROGA F1, JURADO J1, MUSELLA R2, CASTRO Z.L3, BALDINI M2, ABBATE E2 AND GARCIA V1. 1Department of Microbiology and Division of Immunogenetics, School of Medicine, UBA; 2Hospital Muñiz; 3Instituto Vaccarezza, UBA. Effective host defense against Mycobacterium tuberculosis (Mtb) requires Th1 cytokine responses. ICOS, a trans-membrane protein expressed on lymphocytes, promotes T cell proliferation and cytokine production. We investigated the role of ICOS in patients with tuberculosis (TB). Peripheral blood mononuclear cells from TB patients were stimulated with Mtb antigen for 5 days and co-stimulation through ICOS was then performed using anti-ICOS agonistic antibody. Two days later, IFN-g production and T-bet and GATA-3 expression were measured by ELISA and Western blot respectively. In High Responder (HR) TB patients (individuals that display significant Mtb-dependent T cell responses), ICOS ligation in Mtb-stimulated T cells significantly up-regulated IFN-g  production (p<0,005) and T-bet expression, but no changes were observed in IL-10, IL-4 or GATA-3. Moreover, blockade of ICOS/ICOSL pathway by anti-ICOSL antibody decreased IFN-g production in HR TB patients (p<0,05). In contrast, ICOS engagement didn’t modify IFN-g production in Low Responder patients (individuals that show weak T cell responses against Mtb). Furthermore, in human short term polarized T-cell lines, an increase in IFN-g production was detected in Th0 and Th1 cells after Mtb or Mtb+anti-ICOS stimulation. In contrast, neither antigen nor ICOS co-stimulation modified IFN-g secretion by Th2 cells. Our results suggest that ICOS might participate in cell-mediated immune responses to intracellular pathogens.