Sub-apoptotic Concentrations of Galectin-3 Inhibit T-cell

D. FURMAN, G. BIOLEY, E. LEVY, E. VON EUW, M. BARRIO, M. BIANCHINI, C. JANDUS, Y. LI, C. YEE, P. ROMERO, J. MORDOH

Rio de Janeiro (Brasil)

Congreso; 13th International Congress of Immunology; 2007

Galectin-3 (gal-3) is a member of galectins family which has been associated with various biological processes such as cell adhesion, migration, differentiation and apoptosis. This lectin is widely spread among different types of cells, it is either localized in the nucleus and the cytoplasm or secreted via non-classical pathway. An enhanced expression of gal-3 has been found in many human tumor types and is associated with tumor progression. We recently proposed that gal-3 could have an active role in tumor escape mechanisms in melanoma by inducing apoptosis of tumor-associated lymphocytes. In this work we first assessed apoptosis induction by titrated amounts of gal-3 on human cytolytic T-lymphocytes (CTL). CTL clones were heterogenous in their susceptibility to apoptosis upon exposure to gal-3. Next, we studied the effect of sub-apoptotic doses of gal-3 on CTL effector functions. We observed a decreased IFN-ã secretion, degranulation and cytolytic activity when specific CTL clones were activated with cognate peptide in the presence of rGal-3 at 1 and 2 μM; full functional responses were apparent when cells were co-incubated with 5 mM lactose thus indicating the direct role of gal-3 binding to CTL in mediating the inhibition of CTL functions. In conclusion gal-3 not only is able to trigger apoptosis but can also down-regulate CTL functional competence. Our data are consistent with previous observations in KO mice lacking gal-3 binding site, in which T-cells have a lower activation threshold than wild type counterparts. Thus, dysregulation of gal-3 secretion may help tumors to escape from T-cell killing.