Application of recipient-derived dendritic cells to induce donor-specific T-cell hyporesponsiveness

Administration of donor-derived immature dendritic cells (DC) treated with NF-κB oligodeoxyribonucleotides (ODN) prevents allograft rejection. We attempted to explore the use of recipient-derived DC pulsed with donor antigens, in which the donor antigens were presented to host T cells via an indirect pathway (cross-priming). Expression of CD40, CD80, and CD86 on DC was significantly inhibited by treatment with NF-κB ODN, whereas MHC class I and II were minimally affected. Normal C3H DC pulsed with B10 antigens stimulated proliferative responses and donor-specific CTL activity in C3H T cells, both of which were, however, markedly inhibited when DC were treated with NF-κB ODN. This manipulation was associated with reduced IFN-γ and increased IL-10 production in the supernate, suggesting a Th2 bias. More frequent apoptotic T cells were observed in cultures with NF-κB ODN DC. In contrast to administration of normal DC pulsed with donor antigens that accelerated rejection of B10 cardiac allografts (median survival time [MST] 7 days versus 10 days in no-DC treatment control, P < .05), a single injection of 2 × 10⁶ NF-κB ODN DC significantly prolonged allograft survival (MST 50 days, P < .05 compared with no-DC treatment control). The anti-donor CTL activity in infiltrating T cells isolated from cardiac grafts in recipients that received NF-κB ODN DC was significantly suppressed. These data indicate that vaccination with immature DC, propagated from recipient BM is an attractive approach to induce T-cell hyporesponsiveness.