Dual effect of Galectin-8 on human PBMCs: it induces proliferation of naïve T cells but promotes cell death after activation

VALENTINA CATTANEO; MARÍA VIRGINIA TRIBULATTI; OSCAR CAMPETELLA

San Petersburgo, Florida, USA.

Congreso; 2010 Meeting of the Society for Glycobiology; 2010

Society for

Galectin-8 (Gal-8) is a tandem-repeat galectin having two different carbohydrate recognition domains (CRDs) fused by a linker peptide. We have previously shown that Gal-8 induces two distinct effects on mouse TCD4 cells: antigen-independent proliferation and co-stimulation of antigen-specific responses. The molecular requirements for these effects were also studied. We found that dimeric structure was essential only for proliferation, suggesting lattice formation involvement. Co-stimulation instead seemed to be mediated by high affinity agonistic interactions, since it was achieved with either single CRD and could not be inhibited in the presence of lactose. The C-CRD was the primary domain involved in both Gal-8-mediated effects. In the present work, we extended the study of Gal-8 effects to human T cells. PBMCs from healthy donors proliferate in response to 5 microM of Gal-8, but varying from non- to high-responder individuals. This effect was completely abrogated in the presence of lactose, indicating that it was mediated by galectin-glycan interaction. Variations between donor responses could not be ascribed to gender, age or blood group, and all individuals responded to phytohemagglutinin (PHA) stimulation. The absence of proliferation from the non-responder group was not due to cell death induction since no significant increase in the percentage of hipoploidy was observed in Gal-8 treated cells. Moreover, increasing amounts of Gal-8 (up to 40 microM) resulted in a mild proliferation response, indicating that this group was actually more resistant to Gal-8-mediated effect. A mutated protein containing inactivated N-CRD, but not the inactivated-C-CRD, induced strong proliferation of PBMCs, indicating that similarly to mice, the C-CRD was involved. T CD4 cells were also identified as the target cells. Remarkably, Gal-8 promoted cell death of PBMCs from responders and non-responders donors after stimulation with PHA or CD3/CD28. Taken together, these findings support a dual role of this galectin at promoting/limiting the immune response.