ABSTRACT
Objective To investigate the effect and mechanisms of recipient-derived immature dendritic cells(imDC) transfected with IKK2dn and loaded with donor antigen on renal allografts survival in the rats.Methods DC were cultured from recipient rats'(Lewis) bone marrow,transfected with IKK2dn and loaded with donor antigen.The expression of CD86 and MHC Ⅱ was detected,and the ability of DC stimulating lymphocyte proliferation in vitro was measured.Male Brown Norwav rats and Lewis rats were used as donors and recipients respectively.Four groups were set up(DC group,empty transfection group,transfection group and control group),receiving 1×10~7 DC,Adv-0-DC,Adv-IKK2dn-DC loaded with BN antigen,and equal volume of normal saline,respectivelv 7 davs before transplantation.In the third party donor-group,Wistar rats as donors were treated the same as DC;group before transplantation.After transplantation,the T lymphocyte proliferation in reciPients was measured and the expression of serum IL-2 and IFN-γ was detected.The survival time of recipients and the acute reiection were observed.Pathological changes were examined tO identify the grade of rejection.Results DC assessment in vivo revealed that the transfected DC could still express CD86 and MHC Ⅱ in a low level as compared with those not transfected with IKK2dn. After DC were loaded with donor's antigen,the expression of CD86 and MHC Ⅱ was up-regulated.After DC were transfected with IKK2dn before loaded with donor's antigen, the expression of CD86 and MHC Ⅱ had no significant change. When DC were loaded with donor's antigen, its allostimulatory activity of T lymphocyte proliferation was enhanced (P<0. 05). When DC were transfected with IKK2dn before loaded with donor's antigen, its allostimulatory activity of T lymphocyte proliferation was not enhanced. Compared with control groups, IKK2dn-transfected DC pulsed with BN splenocyte lysate markedly prolonged the survival of renal allografts (26. 8±1.76d, P<0.01), and elicited markedly lower proliferative responses and reduced IL-2 and IFN-γ production. The pathological grade of rejection was low in the transfection group. Conclusion Recipient-derived imDC transfected with IKK2dn and loaded with donor splenocyte lysate could prolong the renal allograft survival in rats probably by down-regulating the expression of DC costimulatory molecules and inhibiting the T_H 1 cytokine production.