Programmed Death Ligand-1-Overexpressing Donor Exosomes Mediate Donor-Specific Immunosuppression by Delivering Co-inhibitory Signals to Donor-Specific T Cells.

Programmed death ligand-1 (PD-L1) and donor antigens are critical for donor immature dendritic cells (DCs) targeting donor-specific T cells to induce transplant tolerance. This study aimed to clarify whether DC-derived exosomes (DEX) with donor antigens (H2b) and high levels of PD-L1 expression (DEX PDL1+ ) can help to suppress graft rejection. In this study, we demonstrated that DEX PDL1+ present donor antigens as well as PD-L1 co-inhibitory signals directly or indirectly via DCs to H2b-reactive T cells. This dual signal presentation could prolong the survival of heart grafts from B6 (H2b) mice but not from C3H (H2k) mice by inhibiting T cell activation, inducing activated T cell apoptosis, and modulating the balance of T cell differentiation from inflammatory to regulatory. Additionally, even though DEX PDL1+ treatment could not induce tolerance after short-term treatment, our study provides a new vehicle for presenting co-inhibitory signals to donor-specific T cells. This novel strategy may facilitate the realization of donor-specific tolerance via the further optimization of drug- loading combinations and therapeutic regimens to elevate their killing ability. This article is protected by copyright. All rights reserved.