Apoptosis, proliferative response and costimulatory effect induced by galectin-8 on T cells

MA. VIRGINIA TRIBULATTI1; VALENTINA CATTANEO1; JUAN MUCCI1; TIM GILMARTIN2; STEVEN R. HEAD2; ULF HELLMAN3; OSCAR CAMPETELLA1

Fort Worth, Texas, USA

Congreso; Annual Meeting of the Society for Glycobiology; 2008

Galectins is a family of carbohydrate recognizing molecules ubiquitously expressed in mammals. In the immune system they can regulate many processes such as inflammation, adhesion and apoptosis. By following a microarray approach to analyze the expression of glycosylation-related genes on different cell populations from mouse thymus the transcription of galectin-8, among other genes, was detected both in thymocytes and thymic epithelial cells. Two splice variants were found differing in the insertion of nine aminoacids in the linker region. When assayed on thymocytes, they bound to all subpopulations but induced apoptosis only in the CD4highCD8high cells through caspases pathway activation. In strong contrast, splenocytes displayed robust proliferative response when treated with the lectin, an effect ascribed to T cells. Several integrins and leukocytes surface markers, including CD45 isoforms, were identified as galectin-8 binders by MALDI-Tof analysis. Another binders specific from macrophages, neutrophils and platelets were also characterized. Addition of galectin-8 synergized OVA peptide in splenocytes from TCROVA transgenic mouse even when assayed at doses suboptimal to induce proliferation, denoting an intrinsic costimulatory property in antigen specific T cell activation. Moreover, phosphorylation of ZAP70 and ERK1/2 was triggered then lowering the threshold to activate the TCR signaling pathway. This seems to be associated with the binding to CD45, a known TCR-activator molecule, because pretreatment with CD45 phosphatase inhibitor abolished both naive and antigen-specific proliferative responses. Findings support a distinctive role for locally produced Gal-8 as enhancer of otherwise borderline immune responses and also suggest that might fuel reactivity at inflammatory foci.