Immune Tolerance Effect of Immature Dendritic Cells Cultured Using Low-dose GM-CSF / 대한혈액학회지

ABSTRACT

BACKGROUND: Dendritic cells induce tolerance in the immature state besides the function of antigen presenting cells in the mature state. Using this effect, it will be overcome the rejection in organ transplantation. In this research we are to confirm the tolerance effect and induction mechanism in immature dendritic cell cultured with low-dose GM-CSF. METHODS: Dendritic cells were cultured from BALB/c (H-2d) bone marrow cells in the low concentration of GM-CSF (5U/mL, GM(lo)DC) for 10 days. The phenotype and functional properties of these GM(lo)DC were compared to those of standard BM-DC cultures generated in the high concentrations of GM-CSF (200U/mL) with lipopolysaccharide (GM(hi)DC). RESULTS: Compare to mature DC, GM(lo)DC expressed the low level of CD80 and CD86 and these cells were weak stimulators of allogeneic T cell responses by mixed lymphocyte reaction. The administration of GM(lo)DC prolonged allogeneic skin graft survival (median survival time 11.3+/-1.2 days, compared with 6.6+/-0.8 days in nontreated controls). The effects of these cells were donor specific but couldn't be sustained for a long period. CONCLUSIONS: GM(lo)DC were phenotypically immature and they didn't induce allogeneic T cell responses compared with GM(hi)DC in vitro. It is suggested that the less expression of costimulatory molecule in GM(lo)DC induce the tolerance effect.