ICOS (inducible costimulator) expression correlates with reduced disease severity in tuberculosis.

G. MARTÍNEZ; V. PASQUINELLI; F. QUIROGA; J. JURADO; L. CASTRO ZORRILLA; M. SAAB; L. ALVES; E. ABBATE; V. GARCÍA

Córdoba, Argentina

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

ALAI

ICOS (Inducible costimulator) expression correlates with reduced disease severity in tuberculosis. MARTINEZ G1, PASQUINELLI V1, QUIROGA F1, JURADO J1, CASTRO Z.L2, MUSELLA R3, SAAB M3, Alves L3, ABBATE E3 AND GARCIA V1. 1Department of Microbiology and Division of Immunogenetics, School of Medicine, UBA; 2Instituto Vaccarezza, UBA; 3Hospital Muñiz. IFN-g production by T-cells is crucial for immunity against Mycobacterium tuberculosis (Mtb) infection. ICOS, a trans-membrane protein, promotes T-cell cytokine production. We investigated the regulation of ICOS expression in human tuberculosis (TB). Peripheral blood mononuclear cells from TB patients were stimulated with Mtb for 5 days and ICOS, T-bet (the Th1-specific transcription factor) and GATA-3 (a Th2-specific transcription factor) levels were measured by Flow Cytometry or Western blot. Mtb stimulation significantly increased ICOS levels (4,5±0,8 vs 22.9±2.3) in High Responder TB patients (individual displaying significant Mtb-dependent T-cell responses), up-regulated T-bet and down-regulated GATA-3 levels. In contrast, antigen stimulation didn’t modify ICOS expression (3,7±1,9 vs 5,8±1,9) in Low Responder TB patients (individuals with weak T-cell responses to Mtb), but increased GATA-3 and decreased T-bet levels. Moreover, ICOS was modulated by cytokines during antigen presentation: ICOS and IFN-g levels augmented by pro-inflammatory conditions, whereas they decreased under anti-inflammatory conditions. Furthermore, we evaluated ICOS levels on human polarized short term T cell-lines. We observed high levels of ICOS in Th1 cells (46,6±13,1), intermediate levels in Th0 cells (33,9±10,1), and the lowest expression in Th2 cells (21,3±8,5). These results indicate that differential expression of ICOS in human T cells might influence the outcome of the disease.