Human NK cell activation triggers galectin 1 secretion which regulates the magnitude of IFN- secretion in a CD45-dependent manner

DOMAICA, CAROLINA INÉS; ZIBLAT, ANDREA; SECÍN, FERNANDO; NÚÑEZ, SOL YANEL; TORRES, NICOLÁS IGNACIO; SIERRA, JESSICA MARIEL; RAFFO IRAOLAGOITÍA, XIMENA LUCÍA; SPALLANZANI, RAÚL GERMÁN; CROCI, DIEGO; PÉREZ SAEZ, JUAN MANUEL; FUERTES, MERCEDES BEATRIZ; RABINOVICH, GABRIEL ADRIÁN; ZWIRNER, NORBERTO WALTER

Mar del Plata

Congreso; 64a Reunión Anual de la Sociedad Argentina de Inmunología; 2016

Sociedad Argentina de Inmunología

Galectin-1 (Gal-1) is an endogenousglycan-binding protein widely expressed at sites of inflammation and by tumorcells that controls a diversity of immune cell processes through binding tospecific cell surface glycan structures or through intracellular ill-definedpathways. Gal-1 binds specifically to the cell surface glycoproteins CD45, CD43and CD7. Natural killer (NK) cells trigger cytotoxicity and interferon (IFN)-g secretion upon engagement of activatingreceptors by ligands expressed on tumor cells. Previously we demonstrated that Gal-1 negatively regulates NK cell effectorfunctions. Theobjective of this study was toelucidate the mechanisms involved inthe regulation of NK cell effector functions by Gal-1. To furtherinvestigate this susceptibility, we analyzed the binding of biotinylated Gal-1by flow cytometry to NK cells and observed that Gal-1 binds to resting andactivated NK cells in a carbohydrate-dependent manner, as the addition oflactose inhibited such binding.NK cells activated with cytokines in the presence of Gal-1 and the PTP CD45inhibitor exhibited an equivalent production of IFN-g than cytokine-activated NK cells. Also, byELISA we observedthat NK cells, independently of their activation status secreted Gal-1, butthat activated NK cells exhibited a higher production of Gal-1 than resting NKcells (p<0,005). When isolated NK cells were pre-activated for 5 days withcytokines and re-stimulated with IL-2 in the absence or in the presence ofGal-1 we observed that Gal-1 didn´t inhibit IFN-gsecretion. Collectively, our results suggest that at early stages of activationNK cells secretion of Gal-1 could contribute in a CD45-dependent manner to theregulation of IFN-gsecretion as a mechanism to control excessive activation.