Background AIIogeneic transplant rejection is currently a major problem encountered during organ transplantation. The dendritic cell （DC） is the most effective powerful known professional antigen-presenting cell, and recent studies have found that DCs can also induce immune tolerance, and avoid or reduce the degree of transplant rejection. The aim of this study was to evaluate the effect of transfused immature CD4~ DCs on renal allografts in the rat model. Methods In this study, we induced CD4~ immature DCs from rat bone marrow cells by a cytokine cocktail. The immature CD4~ DCs were identified by morphological analysis and then the suppressive activity of these cells conditioned with donor kidney antigen was evaluated in vitro and in vivo. Results Immature CD4~ DCs conditioned with donor kidney antigen possessed immunosuppressive activity in vitro and they were able to prolong renal transplant survival in an allograft rat model in vivo. Conclusions Our study provides new information on efficacious renal transplantation, which might be useful for understanding the function of immature CD4~ DCs in modulating renal transplant rejection and improving clinical outcome in future studies.
WANG TaoXU LinLI HengHUANG Zheng-yuZHANG Sheng-pingMIAO BinNA Ning
The graft-versus-tumor （GVT） effect of T cells induced by tumor antigen-pulsed CD8α＋ dendritic cells （DCs） in vitro was investigated in this study. Immature CD8c（DCs were prepared from C57BL/6 （H-2b） bone marrow cells by using a cytokine cocktail. On the 3rd day of culture, CD8α＋ DCs were pulsed by allogeneic （Balb/c, H-2d） EL9611 leukemia antigen, or RM-1 syngeneic prostate cancer antigen, with the concentration series of 0, 2.5, 5.0, 10.0, 20.0 μg/mL, respectively, then antigen-loaded immature CD8α＋ DCs were co-cultured with syngeneic T cells according to the DC/T ratio of 1：1, 2：1 and 4：1. T cell proliferation was measured by MTT assay. Cytokines including interferon gamma （IFN-γ） and interleukin-10 （IL-10） in CD8α＋ DCs and T co-culture supernatant were detected by using ELI SA. Cytotoxic effect of antigen-specific T cells was tested by LDH release assay. Conventional mature DCs （mDCs） induced, from C57BL/6 （H-2b） bone marrow cells by using granulocyte-macrophage colony stimulating factor （GM-CSF） and interleukin-4 （IL-4） served as a control. The results showed that the proliferative activity of T cells stimulated by CD8α＋ DCs loaded with allogeneic or syngeneic tumor antigen was augmented with the CD8＆ DC/T ratio increased （P〈0.05）. When antigen concentration 〈 5 μg/mL and CD8a＋ DC/T ratio 〈 2：1, the ability of CD8α＋ DCs to stimulate T cell proliferation was higher than mDC control in allogeneic tumor antigen-pulsed groups （P〈0.05）, but not in syngeneic tumor antigen-pulsed groups （P〉0.05）. The level of IFN-γ and IL-10 in CD8α＋DCs and T cell co-culture supernatant were increased in both allogeneic and syngeneic antigen-pulsed groups （P〈0.05）, and the cytokine level was higher in allogeneic antigen-pulsed groups than in syngeneic antigen groups when the CD8α＋ DC/T was 1：1 or 2：1 （P〈0.05）. There existed a negative correlation between the level of IL-10 and T cell proliferation. T cell cytotoxi
