In vivo migration and immunoprotection of interleukin-10-modified dendritic cells in rats after heterogenic simultaneous liver-kidney transplantation

Suxiong DENG; Junliang LI; Yi MA

ABSTRACT

BACKGROUND:

Donor antigen presenting cells immigrated into the recipient can induce the immunological tolerance of recipient T cells to donor, leading to a final acceptance to grafts, lnterleukin-10 (IL-10) modification maintains dendritic cells at a desirable differentiating state, which is an effective method to promote the protection to kidney in the simultaneous liver-kidney transplantation.

OBJECTIVE:

To observe the immigration of IL-10-modified dendritic cells in rats subjected to simultaneous liver-kidney transplantation and to investigate the mechanism of action.DESIGN, TIME AND

SETTING:

A randomized, controlled, animal experiment was performed in the Medical College of Sun Yat-sen University between June 2004 and February 2006.MATERIALS Male DA donor rats (n=60) and Lewis recipient rats (n=60), both were adult and of clean grade, were included.Sixty Lewis rats were randomly and evenly divided into 3 groups IL-10-modified cell group, simple cell group, and model control group.

METHODS:

Donor rat liver and kidney were harvested by simultaneous liver-kidney transplantation. Recipient rats in each group were subjected to orthotopic liver and left kidney transplantation to establish models of immunological rejection. Under sterile condition, donor rat femur and tibia were harvested. Dnlbecco's modified eagle's medium (DMEM) was used to wash out the bone marrow. After removal of red cells, dendritic cells were isolated and cultured by adherent method. After modified with 20 μg/L IL-10 for 72 hours, dendritic cells were intravenously transfused into rat bodies in the IL-10-modified group, 2×10(7) cells/rat, In the simple cell group, rats were treated with donor dendritic cells without modification with IL-10. Rats in the model control group received no any interventions.MAIN OUTCOME

MEASURES:

[1]Dynamic changes of vital sign, urine volume, liver and renal function in recipient tissues;[2] Pathohistological detection results;[3]Distribution of donor dendritic cells in the recipient rats by in situ hybridization.

RESULTS:

In the simple cell and model control groups, urinary volume was reduced to 0 mL 5-6 days after transplantation. In addition, both groups presented with severe acute rejection. In the IL-10-modified cell group, urinary volume maintained at 6-12mL within 2 weeks after transplantation. The acute rejection of liver and kidney transplantation was obviously inhibited, surviving for(20.0±2.6) days on average, which was significantly longer than that in the simple cell group and model control group. A probability value of less than 0.05 in the Log Rank test was considered statistically significant. There were many Y chromosome-labeled dendritic cells immigrated into the mesenteric lymph node in the recipient rats.

CONCLUSION:

IL-10-modified dendritic cells play an immunoprotective effect on the liver and kidney transplanted simultaneously. Donor immature dendritic cells immigrated into recipient tissue could reduce acute rejections and prolong the survival time of liver and kidney grafts and recipients.