Autor/es:
CARABELLI, J; PRATO, CA; SANMARCO, LM; AOKI, MP; CAMPETELLA, O; TRIBULATTI, MV
Resumen:
Galectin-8 (Gal-8) is a mammalian lectin endowed with the ability to co-stimulate the antigen-specific immune response. IL-6
is a pleiotropic cytokine that plays an important role in the regulation of antigen-specific T cell response. In the present study, we
aimed to elucidate whether IL-6 was mediating Gal-8 costimulatory effect on antigen-specific CD4T cells. Firstly, we quantified IL-6
by ELISA in supernatants from DO11.10TCR
OVA
mouse splenocyte
cultures, stimulated with the cognate peptide OVA(OVA), Gal-8 or
the combination of both. Notably, IL-6 was significantly increased
in the conditioned media from Gal-8- or Gal-8 plus OVA-treated
cells but not from OVA only-treated cells, where IL-6 was present
at the same level as in untreated cells. Next, to assess if IL-6 is
involved in Gal-8 costimulatory effect, splenocytes were stimulated,
as before, but in the presence of an IL-6-neutralizing monoclonal
antibody or a matching isotype control, and T cell proliferation was determined. Interestingly, IL-6 neutralization specifically precluded
Gal-8 costimulatory activity but did not affect antigen-specific T cell
response. To identify those cells that produce IL-6 in response to
Gal-8, intracellular IL-6 was determined by FACS in Gal-8-stimulated BALB/cJ splenocytes. We found that both CD11c
+
and CD11b
+
cells produced IL-6 in response to Gal-8. Finally, to confirm that IL-6
from antigen-presenting cells was mediating the Gal-8 costimulatory
effect, splenocytes from IL-6-deficient (IL6KO) or C57BL/6J (wildtype) mice pre-treated with Mitomycin-C, were co-cultured with purified CD4T cells from OTII mice in the presence of OVA, Gal-8 or
the combination of both. In agreement, Gal-8-induced costimulation
of antigen-specific CD4T cell response was significantly impaired
when APC from IL-6KO mice were used. Taken together, our results
argue in favor of the participation of IL-6 in the immunostimulatory
pathway induced by Gal-8.