Cell therapy using tolerogenic dendritic cells in transplantation

Abstract

Organ transplantation is the main alternative to the loss of vital organ function from various diseases. However, to avoid graft rejection, transplant patients are treated with immunosuppressive drugs that have adverse side effects. A new emerging approach to reduce the administration of immunosuppressive drugs is to co-treat patients with cell therapy using regulatory cells. In our laboratory, as part of a European project, we plan to test the safety of tolerogenic dendritic cell (TolDC) therapy in kidney transplant patients. In this mini-review, we provide a brief summary of the major protocols used to derive human TolDC, and then focus on the granulocyte macrophage-TolDC generated by our own team. Proof of safety of TolDC therapy in the clinic has already been demonstrated in patients with diabetes. However, in transplantation, DC therapy will be associated with the administration of immunosuppressive drugs, and interactions between drugs and DC are possible. Finally, we will discuss the issue of DC origin, as we believe that administration of autologous TolDC is more appropriate, as demonstrated by our experiments in animal models.

Figure 1

Influence of culture medium on human dendritic cell differentiationin vitro. Four populations of DC were generated in two different culture media, either RPMI/albumin or AIMV and with two different cytokine conditions, either low-dose GM-CSF (GM-DC) or GM-CSF and IL-4 (Control DC) for 6 days. (A) The four DC populations were cultured with allogeneic T cells at different ratios for 6 days. A representative experiment is shown on the left-hand panel. On the right, the results of the ratio of one DC to four Tcells are expressed as the mean T cell proliferation + standard error of the mean for three different donors (*** P < 0.001, paired T tests). (B) The four populations were un-stimulated (grey solid histogram) or stimulated with 200 ng/mL LPS and 50 ng/mL IFN-γ (black line) for 48 hours. Cell surface expression of CD80, CD83 and CD86 was analyzed after 48 hours of culture by flow cytometry. Data shown are representative of two experiments performed.