Donor dendritic cells treated with B7- 1, B7- 2 antisense oligonucleotide prolonged mouse cardiac allograft survival / 中国病理生理杂志

ABSTRACT

AIM:To investigate the effect of donor bone marrow derived dentritic cell (DC) treated with B7 - 1, B7 - 2 antisense oligonucleotide on mouse heart allografe survival time and its mechanism. METHODS: There were 7 groups of C57BL/10J (B10) mouse bone marrow DCs which were treated by 400 nM antisense oligonucleotide target to B7 -1, B7 -2 mRNA (AS B7- 1/2), B7- 1 mismatch oligo control ,B7- 2 mismatch control(mASB7- 1/2), lipofeetamine only and non-treatment, respectively. Each group of DC were named as ASB7- 1 DC, ASB7- 2 DC, mASB7 - 1 DC, mAS B7 - 2DC, and Lipo DC, respectively. RESULTS: Flow cytometer results shown that AS B7- 1/2 can inhibit B7- 1 (CD80)and B7- 2 (CD86) molecule express on DC surface, while control groups have no effects. To observe their tolerogenicity in mouse cardiac allograft model, B10→C3H heterotopic heart transplantation were performed. Recepients were received 2 x 106 of DC injection 7 days before transplantation. Results showed that both AS B7 - 1 DC and AS B7 - 2 DC can prolong mouse cardiac allograft survival time to (18.6 + 0.89) days and (23.67 + 10.73) days, respectively, compared with IL - 4 DC [ (6.22 + 0.97) days ( P < 0.01 ) ]. Two mismatch control groups can slightly prolong while oligo DC has no effect. For understanding its mechanism, each group of DC was used as stimulator to stimulated C3H spleen T cell. Results suggested that AS B7 - 1DC and AS B7 - 2 DC had less allo - stimulate function, including MLR and generation CTL and IL - 2 production than IL - 4 DC but control groups have no effect. CONCLUSION: Donor bone marrow derived DC treated with AS B7 - 1 oligo and AS B7 - 2 oligo expressed lower level of CD80 and CD86, respectively. These cells can induce allogeneic T cells anergy in vitro and markedly prolong mouse heart allograft survival time in vivo.