The synergic effects of sirolimus and immature dendritic cells in prolonging survival time of skin allograft in mice

Objective T To investigate the effect of sirolimus (SRL) on the differentiation,development,and maturation of mice bone marrow-derived dendritic cells (DC),and the synergic effects of them in prolonging survival time of skin allograft.Methods (1) DC of C57BL/6 mice were derived from bone marrow cells upon culture with SRL. The expression of CD11c,CD86 and major histocompatibility complex (MHCⅡ) molecules was assessed with or without lipopolysaccharide (LPS) stimulation by flow cytometry; (2) The capacity of DC administrated by SRL to stimulate allogeneic T lymphocyte proliferation was examined by mixed lymphocyte culture (MLR); (3) A skin transplantation model was established with the recipients BALB/c mice and the donor C57BL/6 mice. Recipients were divided into control group (there was no administration before skin transplantation),immature DC group (injection of donor C57BL/6 mice immature dendritic cells 2×10 6 via tail vein before skin transplantation),SRL group (receiving oral SRL 3 mg/kg every day for 7 days before skin transplantation),combined group (receiving an injection of donor C57BL/6 mice immature DC via tail vein and of oral SRL before skin transplantation),and isogeneic group (in which the donors and recipients were both BALB/c mice and there was no administration before skin transplantation). Survival time and histological changes of skin allograft were observed in different groups.Results (1) CD11c expression on the DC in the presence of SRL was slightly decreased,but CD86 and MHCⅡ molecules significantly decreased,and SRL treatment could resist the stimulation of LPS; (2) MLR revealed that DC administrated by SRL could inhibit allogeneic T lymphocyte proliferation; (3) SRL treatment in combination with donor immature DC before transplantation could alleviate inflammation and prolong survival time of skin allograft in mice.Conclusions SRL does not alter differentiation but inhibit the maturation of DC. Sirolimus can cooperate with immature DC to prolong survival time of skin allograft in mice.