IL-10-Engineered Dendritic Cells Modulate Allogeneic CD8 T Cell Responses.

Tolerogenic dendritic cells (tolDC) play a central role in regulating immune homeostasis and in promoting peripheral tolerance. These features render tolDC a promising tool for cell-based approaches aimed at inducing tolerance in T-cell mediated diseases and in allogeneic transplantation. We developed a protocol to generate genetically engineered human tolDC overexpressing IL-10 (DC) by means of a bidirectional lentiviral vector (LV) encoding for IL-10. DC promote allo-specific T regulatory type 1 (Tr1) cells, modulate allogeneic CD4 T cell responses in vitro and in vivo, and are stable in a pro-inflammatory milieu. In the present study, we investigated the ability of DC to modulate cytotoxic CD8 T cell responses. We demonstrate that DC reduces allogeneic CD8 T cell proliferation and activation in primary mixed lymphocyte reactions (MLR). Moreover, long-term stimulation with DC induces allo-specific anergic CD8 T cells without signs of exhaustion. DC-primed CD8 T cells display limited cytotoxic activity. These findings indicate that stable over-expression of IL-10 in human DC leads to a population of cells able to modulate cytotoxic allogeneic CD8 T cell responses, overall indicating that DC represent a promising cellular product for clinical applications aimed at inducing tolerance after transplantation.