Interleukin-10 modified dendritic cells induce allo-hyporesponsiveness and prolong small intestine allograft survival

Abstract

AIM:To investigate whether IL-10-transduced dendritic cells (DCs) could induce tolerogenicity and prolong allograft survival in rat intestinal transplantation. METHODS:Spleen-derived DCs were prepared and genetically modified by hIL-10 gene. The level of IL-10 expression was quantitated by ELISA. DC function was assessed by MTT in mixed leukocyte reaction. Allogeneic T-cell apoptosis was examined by flow cytometric analysis. Seven days before heterotopic intestinal transplantation, 2×10 6 donor-derived IL-10-DC were injected intravenously, then transplantation was performed between SD donor and Wistar recipient. RESULTS:Compared with untransduced DC, IL-10-DC could suppress allogeneic mixed leukocyte reaction (MLR). The inhibitory effect was the most striking with the stimulator/ effector (S/E) ratio of 1:10. The inhibition rate was 33.25 %, 41.19 % (P<0.01) and 22.92 % with the S/E ratio of 1:1, 1:10 and 1:50 respectively. At 48 hours and 72 hours by flow cytometry counting, apoptotic T cells responded to IL-10-DC in MLR were 13.8 % and 30

Biology of interleukin-10 and its regulatory roles in sepsis syndromes

“…Mice reconstituted with these cells also survived a septic challenge, suggesting that this may be a therapeutic approach for sepsis. Other investigators have shown that IL-10-transduced DCs also prolonged survival in rats in a model of transplant rejection, indicating that their use may be beneficial in other models of injury (37)(38)(39). Whether these cells directly or indirectly produce the protective effects and whether these effects can be recapitulated using the different types of regulatory cells needs to be further examined.…”

A Key Role of Dendritic Cells in Probiotic Functionality

“…Indeed, a recent in vitro study demonstrated that lactobacilli, in a strain-specific manner, were able to prime DCs to promote the development of Treg cells through DC-SIGN interaction [16]. Recent studies have shown that the conversion of DCs to tolerogenic DCs could lead to the inhibition of NFκB [17] and could be used therapeutically to prevent allograft rejection [18]. One of the mechanisms exploited by tolerogenic DCs involves expression of indoleamine 2, 3 dioxygenase (IDO), a tryptophan-catabolizing enzyme that can exert regulatory effects on T cells by tryptophan depletion [19], [20].…”

Long-Term Survival of Limb Allografts Induced by Pharmacologically Conditioned, Donor Alloantigen-Pulsed Dendritic Cells Without Maintenance Immunosuppression

“…Certain DC populations are thought to induce tolerance via the induction of Treg, T-cell deletion by promotion of apoptosis, or skewing of T cells towards a Th2 subtype (18 -21). Efforts to promote DC tolerogenicity include their exposure to immunosuppressive cytokines, such as interleukin (IL)-10 and transforming growth factor (TGF)-␤ or to pharmacological agents, that arrest their maturation, or gene delivery to enhance the expression of a variety of immunosuppressive molecules (22)(23)(24)(25). Among the pharmacological agents, rapamycin (Rapa) appears to be a good candidate for suppression of DC maturation and the generation of DC with immunoregulatory function (16,26).…”