Immune tolerance induced by immature dendritic cells treated with tacrolimus in rat heart transplantation

Guiming ZHANG; Xianghua WANG; Lijiang SUN

ABSTRACT

BACKGROUND:

Immune tolerance is regarded as the most effective measure to overcome rejection. For the past few years, the important effect of immature dendritic cells (imDCs) on immune tolerance has drawn close attention.

OBJECTIVE:

To study the effect of imDCs treated with tacrolimus (FK506) on imlnune tolerance in rat allograft organ transplantation and to investigate the mechanism of immune tolerance induced by imDCs.

DESIGN:

A randomized and controlled animal experiment. MATERIALS The experiment was carried out at the Experimental Animal Center, the Affiliated Hospital of Medical College. Qingdao University from April 2006 to December 2006.Cervical heart transplantations were performed in which 45Wister rats were used as donors and45 SD rats as allograft recipients. The ratswere randomly divided into three groups with 15 for each.

METHODS:

Normal sodium, imDes. and imDCs treated with FK506 were injected via vena caudalis seven. days before the operations respectively. Mixed lymphocyte reaction (MLR) was meas ured on SD, Wistar, and Lewis rats. MAIN OUTCOME

MEASURES:

Heart allografi survival was monitored and one-way MLR, heart pathology and the levels of interleukin-2(IL-2),IL-4,IL-10,and interferon-Y(IFN-Y)in the serum were detected.

RESULTS:

In treatment group without FK506.heart allografl survival were prolonged after imDC injection(P＜0.01);while their survival were prolonged further in treatment group with FK506(P＜0.05).MLR showed that the tolerance was donor specific. Analysis of variance showed that tere was high significant difference for serum concentrations of IL-2,IFN-Y,IL-4,and IL-10 in the three groups(P＜0.01).The concentrations of IL-2 and IFN-Y expressing on Th1 were lower. and that of IL-4 and IL-10 expressing on Th2 were obviously higher in the latter two groups.

CONCLUSION:

ImDCs can induce immune tolerance in rat heterotopic heart transplantation successfully; ImDCs treated with FK506 can enhance the tolerance which is donor specific.ImDCs may induce the immnune tolerance bymeans of modifying the immune response type of T cells (immune deflection from Th1 to Th2), mediating the generation of regulatory T cells (T-reg)and inducing T cells disenabling.