ABSTRACT
Objective To investigate the effect of regulatory dendritic cells treated by extracorporeal photochemotherapy on T cell proliferation. Methods Human peripheral blood mononuclear cells (PBMCs) were obtained and the immature dendritic cells (imDCs) were induced by recombinant human granulocyte and macrophage colony stimulating factors. SPDCs were obtained by PUVA treatment, and ECDCs were co-cultured with imDCs and PUVA-SP to obtain immunoprecipitated dendritic cells. In vitro, imDCs were co-cultured with SPDCs to obtain SPDCs; imDCs were added to 10ng/ml of LPS, and cultured for 1 day to obtain DCs. The expressions of CD11c, CD83 and CD86 on the surface of the cells were detected. The effect of imDCs on the proliferation of recipient T cells was detected by mixed lymphocyte culture method. Results The early apoptosis rate of PUVA-treated cells was 91.33%. The positive expression rates of CD83 and CD86 in ecpDCs were 22.83%±5.26% and 22.06%±4.37%, respectively, which were similar to those of imDCs (15.06%±0.59%, 15.19%±1.83% (P<0.01), but significantly lower than those in DCs (99.79%±0.36%, 99.85%±0.19%, respectively), the difference was statistically significant (P<0.01). The recipient imDC cells phagocyting the appoptotic splenic lymphocytes from the donor significantly inhibited the proliferation of recipient T cells. Conclusion Apoptosis of splenic lymphocytes induced by extracorporeal photochemotherapy can inhibit the maturation of dendritic cells and inhibit the proliferation of T lymphocytes.
ABSTRACT
Objective To analyze the correlation of tumor recurrence after liver transplantation for hepatocellular carcinoma (HCC)with the expression levels of regulatory T cell (Treg)and cytokines in peripheral blood. Methods A total of 56 patients who underwent liver transplantation in the 309th Hospital of People's Liberation Army from 2010 to 2014 were studied. According to the postoperative pathological data,all the patients were divided into the group of liver transplantation for HCC (HCC group,n=28)and group of liver transplantation for cirrhosis (liver cirrhosis group,n=28), of which the HCC group was further divided into non-recurrence group (n=8)and recurrence group (n=20)according to the situation of postoperative tumor recurrence. The expression levels of Treg and cytokines [vascular endothelial growth factor (VEGF),interleukin (IL)-2,IL-10,IL-12,transformation growth factor (TGF)-βand interferon (IFN)-γ]in peripheral blood of the patients in various groups were compared. Results Compared with the liver cirrhosis group,levels of IFN-γand IL-12 in the non-recurrence group increased significantly (both P<0.05);levels of Treg%,VEGF,IFN-γ, IL-10 and TGF-βin the recurrence group increased significantly,while levels of IL-2 and IL-12 decreased significantly (all P<0.05). Compared with the non-recurrence group,levels of Treg%,VEGF,IL-10 and TGF-βin the recurrence group increased significantly,while levels of IFN-γ,IL-2 and IL-12 decreased significantly (all P<0.05 ). Conclusions Levels of Treg and cytokines can be used to predict the tumor recurrence after liver transplantation for HCC.
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Objective To investigate the effect of infusion of spleen lymphocytes treated by extracorporeal photochemotherapy on the regulatory T cell (Treg)and survival time of skin allograft in mice. Methods The skin allograft model in mice was established with C57BL/6 mice as donors and BALB/c mice as recipients. The spleen lymphocytes (CSP,BSP)in mice C57BL/6 and BALB/c were isolated,and the mice spleen lymphocytes (PUVA-SP) treated with 8-methoxypsoralen plus ultraviolet (PUVA)were prepared. The experimental animals were randomly divided into 5 groups according to the compositions infused into the recipients through vein:PUVA-BSP,PUVA-CSP,BSP,CSP and phosphate buffer solution (PBS)control groups (n=12 in each group). All recipients of each group were injected with PUVA-BSP,PUVA-CSP,BSP,CSP or PBS on day 7 before the operation,on the operation day and day 7 after the operation through the tail vein,respectively. The survival time of graft in the recipients was observed,and the expression of CD4 +CD25 +Foxp3 +Treg in peripheral blood was detected. Results After skin allograft,the rate of CD4 +CD25 +Foxp3 +Treg in peripheral blood of the recipients in PUVA-BSP group and PUVA-CSP group was significantly higher than those of BSP, CSP and PBS control groups. The rate of CD4 +CD25 +Foxp3 +Treg in PUVA-CSP group was higher than that of PUVA-BSP group,while BSP and CSP groups were lower than that of PBS control group. The survival time of skin graft in the recipients in PUVA-BSP group and PUVA-CSP group was significantly longer than that of BSP,CSP and PBS control groups (all P<0.05 ). Conclusions Sufficient infusion of PUVA-SP can induce more CD4 +CD25 +Foxp3 +Treg in the recipients and prolong survival time of skin graft significantly.
ABSTRACT
Objective To discuss the relationship between Foxp3 +regulatory T cell (Treg)and tumor recurrence of patients after liver transplantation for primary hepatocellular carcinoma (HCC) over University of California,San Francisco (UCSF)criteria.Methods Clinical data of 24 patients with HCC undergoing liver transplantation in the Organ Transplantation Research Institute of the 309 th Hospital of People's Liberation Army from January 2010 to December 2013 were retrospectively studied.During the follow-up,4 patients recurred (tumor recurrence group)and other 20 patients did not recur (tumor non-recurrence group).The blood samples of healthy people was selected as control group at the same period.The levels of alpha-fetoprotein (AFP)were compared at different time points of the recurrence group and the non-recurrent group before and after transplantation.The levels of Foxp3 +Treg (Foxp3 +Treg%)were compared at different time points of the tumor recurrence group,the tumor non-recurrence group and the control group before and after transplantation.The relations between expression of Foxp3 +Treg and the levels of AFP,CD3 + and CD8 +T before and after transplantation were analyzed by correlation analysis.Results Compared with the level of Foxp3 +Treg before transplantation and the normal level,the expression of Foxp3 +Treg of patients in tumor non-recurrence group after transplantation firstly decreased,then gradually increased and finally stabilized at a low level.Compared with patients in tumor non-recurrence group,the levels of AFP and Foxp3 +Treg of patients in tumor recurrence group increased obviously and were significantly higher than the normal levels (both in P <0.01).Moreover,abnormal increase of Foxp3 +Treg at early stage was prior to AFP among the patients in tumor recurrence group.Correlation analysis indicated that the change of Foxp3 +Treg was consistent with the changes of AFP,which was positively correlated (P <0.01).But the change of Foxp3 +Treg was contrary to the change of effector T cells (CD3 +T cells and CD8 + T cells),which was negatively correlated (P <0.05-0.01).Conclusions Foxp3 +Treg is closely associated with tumor recurrence after liver transplantation for HCC.In the patients after liver transplantation for HCC over UCSF criteria,the higher Foxp3 +Treg is,the higher the recurrence risk is.Joint detection of AFP is beneficial to find tumor recurrence.
