ICOS (Inducible Costimulator) expression correlates with reduced disease severity in tuberculosis

MARTINEZ GUSTAVO; PASQUINELLI, VIRGINIA; QUIROGA, MARÍA F; JURADO, JAVIER O; CASTRO ZORRILLA, LILIANA; MUSELLA, ROSA; SAAB, MARÍA; ALVES, LEANDRO; ABBATE, EDUARDO; GARCÍA, VERÓNICA E

Córdoba, Argentina

Congreso; VII Congreso Latinoamericano de Inmunología; 2005

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.