Galectin-8 provides costimulatory and proliferative signals to T lymphocytes

MARÍA VIRGINIA TRIBULATTI; VALENTINA CATTANEO; ULF HELLMAN; JUAN MUCCI; OSCAR CAMPETELLA

JOURNAL OF LEUKOCYTE BIOLOGY

FEDERATION AMER SOC EXP BIOL

Año: 2009

0741-5400

Galectins constitute a family of carbohydrate recognizing molecules ubiquitously expressed in mammals. In the immune system they regulate many processes such as inflammation, adhesion and apoptosis. Here we report the expression in the spleen of the two same Galectin-8 (Gal-8) splice-variants previously described in the thymus. Gal-8 was found to induce two separate biological activities on T lymphocytes: a robust naive CD4+ T cell proliferation in the absence of antigen and, notably, a costimulatory signal that synergized the cognate OVA peptide in DO11.10 mice transgenic for TCROVA. The antigen-independent proliferation induced by Gal-8 displayed increased expression of both pro- and anti-inflammatory cytokines, thus suggesting the polyclonal expansion of both Th1 and Th2 clones. The costimulatory effect on antigen specific T cell activation was evidenced when both the galectin and the peptide were assayed at doses suboptimal to induce T cell proliferation. By mass spectra analysis, several integrins and leukocytes surface markers, including CD45 isoforms, as well as other molecules specific to macrophages, neutrophils and platelets were identified as putative Gal-8 counter-receptors. Gal-8 triggered ZAP70 and ERK1/2 phosphorylation. Moreover, pretreatment with specific inhibitors of CD45 phosphatase or ERK1/2 prevented both its antigen-dependent and independent T-cell proliferative activities. This seems to be associated with the agonistic binding to CD45, which lowers the activation threshold of the TCR signaling pathway. Taken together, our findings support a distinctive role for locally produced Gal-8 as an enhancer of otherwise borderline immune responses and also suggest that Gal-8 might fuel the reactivity at inflammatory foci.