“Competitive and/or additive effects are observed in the interaction of Galectins -1, -3 and -8 on T cells”.

FIGINI, MARÍA GABRIELA; TRIBULATTI, MARÍA VIRGINIA; CAMPETELLA, OSCAR

Lake Louise, Alberta

Congreso; New Frontiers at the Interface of Immunity and Glycobiology.; 2011

Keystone Simposia

Galectins constitute a family of mammalian lectins that are emerging as relevant mediators of the immune system response. We have previously reported a proliferative and co-stimulatory activity on mouse splenocytes for Galectin-8 (Gal-8), a member of the tandem-repeat group with two carbohydrate recognition domains (CRDs) fused by a linker peptide. Moreover, we have recently shown that Gal-8 proliferative effect relays upon its bivalent-structure whereas the co-stimulatory effect could be achieved with either N- or C- single CRDs. These findings prompted us to investigate if proto- and chimera type galectins, which contains only one CRD, can also mediate these effects. Gal-1 and -3 are two major representative members of galectin family, and their roles in the immune system have been extensively studied, however, there is scarce information regarding their activity on naïve T lymphocytes. We found that, in contrast to Gal-8, neither Gal-1 nor Gal-3 induced proliferation of mouse splenocytes, meanwhile Gal-1 partially inhibited Gal-8-induced proliferation. Interestingly, we observed that Gal-1, but not Gal-3, co-stimulated the specific response to OVA cognate-peptide in the DO11.10 TCROVA mouse model, in a dose-dependant manner (from 0.5 to 20 mM). Moreover, the presence of Gal-3 inhibited both Gal-1 and Gal-8 co-stimulatory activities. The results described here are in agreement with the structural requirements we have previously reported for Gal-8 because Gal-1, with only one CRD, shared the co-stimulatory but not the proliferative activity. It is known that Gal-3 increases the TCR activation threshold, thus providing a plausible explanation for the absence of co-stimulation. In fact, we observed a reduced response to OVA cognate-peptide in the presence of Gal-3. Taken together, these data reveal a novel co-stimulatory property for Gal-1 on the antigen-specific T cell response; and at the same time highlight the presence of an opposite activity for Gal-3.