Post-transcriptional CD59 gene silencing by siRNAs induces enhanced human T lymphocyte response to tumor cell lysate-loaded DCs

CD59 is a complement regulatory protein known to prevent the membrane attack complex (MAC) from assembling. To investigate the role of CD59 molecules in human T cell activation in response to exogenous antigens, gene silencing via small interfering RNAs (siRNAs) was carried out. Subsequent T cell activation in response to both autologous dendritic cells (DCs) loaded with tumor lysate and beads coated with anti-CD3, anti-CD28 and anti-CD59 antibodies was investigated. The findings demonstrated that decreased CD59 expression on T cells significantly enhanced activation and proliferation of CD4+ T cells and CD8+ T cells while the expansion of CD4+ CD25+ regulatory T cells (Tregs) was not affected, and CD59 mediated inhibition of T cell activation requires the binding of CD59 with its ligand on antigen-presenting cells (APCs). The data support that CD59 down-regulates antigen-specific activation of human T lymphocytes in a ligand-dependent manner.

► We generate human T cells which CD59 gene expression is suppressed by siRNAs.
► CD59 engagement with its soluble ligand fails to impact on T cell activation.
► CD59 inhibits T cell activation in response to exogenous antigens.
► CD59 plays its inhibitory role when antigen recognition takes place.
► The mechanism relies on the binding of CD59 molecules to their ligands on APCs.