TOLL-LIKE RECEPTOR-MEDIATED CD155 EXPRESSION REGULATES CPG MEDIATED TH1/TH2 IMMUNITY

Abstract

CD155 is a ligand for the activating receptor DNAM-1, which is constitutively expressed on most immune cells. Binding of CD155 to DNAM-1 induces NK cell and CD8+ T cell-mediated cytotoxicity and cytokine secretion. Here we show that CD155 is induced by Toll-like receptor activation on antigen-presenting cells. MYD88/TRIF was sufficient to induce the expression of CD155. Ligand upregulation was prevented by pharmacological and genetic inhibition of NF-¿B. Furthermore, TRIF-induced CD155 upregulation was enhanced by IRF3. We also show that CD155 modulates TH1 antibody responses induced by CpG stimulation in vivo. CD155 deficient mice produced increased IgG2a/c titers in response to a protein antigen and CpG when compared to wild type mice. Our data suggest that CD155 promotes the differentiation of CD4+ T cells towards a TH2 phenotype and point towards CD155 as a novel target for vaccination protocols aiming to enhance protective humoral immunity.