Central tolerance induction by adoptive transfer of donor dendritic cells (145.5)

Abstract

Abstract The principal function of DCs is to promote T cell activation and differentiation into effecter T cells by presenting foreign Ags and providing costimulatory signals. DCs also play a critical role in maintaining not only peripheral but also central tolerance. Central tolerance is established by negative selection of developing T cells that have high-affinity TCRs for self-peptide-MHC complexes expressing on DCs or mTECs. We studied whether i.v. injection of allogeneic DCs that are obtained BM culture with Flt3L (FLDCs), GM-CSF(GMDCs) or allogeneic B cells could home to the recipient thymus. We found that only FLDCs could traffic to the recipient thymus. In MLR assay, splenic T cells and mature thymocytes which were recovered from donor FLDCs infused mice, have poor proliferative activity in response to donor APCs, whereas the responses of T cells against third party APCs were as same as control mice. The MHC classI Ld specific 2C thymocytes were selectively deleted after intravenous injection of BALB/c FLDCs. Furthermore, adoptive transfer of donor FLDCs showed significant prolonged donor skin graft. FLDCs transfer was also able to prolong the donor islet graft and prevented the mice from streptozotocin induced diabete mellitus. These results show that i.v injection of FLDCs induces donor specific both central and peripheral tolerance.