The Differential Effects of Donor-Strain Immature Dendritic Cell Subtypes and the Blockade of CD40/CD154 Pathway on the Creation of Allograft Tolerance / 대한신장학회잡지

ABSTRACT

BACKGOUND Dendritic cells (DC) are pivotal antigen presenting cells and serve a unique role in initiating immunity. To test the hypothesis that pre-immunization of recipient with certain DC subsets of donor origin can influence graft outcome. METHODS: We have studied the effects of immunization with allogeneic CD4+CD11c+(MDC) and CD8+CD11c+(LDC) DCs on the allograft response. RESULTS: Both immature MDC and LDC subsets from DBA/2 were able to prime naive allogeneic C57BL/6 (B6) T cells in MLR. In vitro allogeneic T cell responses were attenuated by the addition of anti-CD154 mAb into the culture. T cells from B6 mice that received DBA/2 MDC intravenously 4 weeks before testing mounted weaker MLR driven cell proliferation than T cells from LDC pretreated B6 mice. Consistent with the MLR results, combined pretreatment with MDC, but not LDC, plus anti-CD154 mAb produced donor-strain specific long-term graft survival and induced tolerance while treatment with LDC plus anti-CD154 mAb created minimal prolongation of allograft survival in a pancreas islet transplant model (DBA/2->B6). The beneficial effects exerted by MDC and anti-CD154 mAb pretreatment were correlated with TH1 to TH2 immune deviation and with the amplified donor-specific suppressive capacity by recipient CD4+CD25+T cells. CONCLUSION: These findings highlight the capacity of MDC to modulate alloimmune responses, and suggest therapeutic approaches for the induction of donor specific tolerance.