Galectin-8 induces T cell proliferation via CD45 signalling pathway

VALENTINA CATTANEO, MARÍA VIRGINIA TRIBULATTI, JUAN MUCCI, ULF HELLMAN Y OSCAR CAMPETELLA

Mar del Plata, Buenos Aires, Argentina.

Congreso; XLIII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2007

Galectin-8 (Gal-8) was recently shown to be present in mouse thymus and to induce apoptosis of the CD4high CD8high subpopulation. In the present work, we wanted to explore its role on mature lymphocytes. First, the two splice varians (Gal-8S and Gal-8L) were cloned from mouse splenocytes and protein expression was confirmed by Western-blot. When recombinant Gal-8 was added to splenocyte cultures, a strong proliferation was observed. The highest proliferation rate was achieved with Tcell enriched cultures, thus identifying them as them as the principal target. Furthermore, a Th1/Th2 profile was obtained with Gal-8 treated splenocytes by RT-PCR.  In Order to find potential binders, mouse splenocytes extracts were subjected to Gal-8-affinity chromatography followed by MALDI-Tof assay. Interestingly, CD45 a known coestimulator in the TCR signalized activation was one of the identified binders. Therefore, its possible involvement in Gal-8 proliferation iduction was tested. An inhibitor of the protein tyrosine phosphatase activity of the CD45 included in splenocyte cultures together with Gal-8, substantially reduced the proliferation rate. Moreover, Gal-8 was able to induce p44 and p42 MAPK phosphorylation in Jurkat T cells, demonstrating the activation of the CD45 intracellular cascade. Clearly, these results make evident the involvement of CD45 in Gal-8-induced Tcell proliferation.