The immune regulatory effect of apoptotic cells and exosomes on dendritic cells: Its impact on transplantation

Dendritic cells (DC) are professional antigen (Ag) presenting cells (APC) that trigger the anti-donor T-cell response that causes allograft rejection. During the past decade several laboratories have employed in vitro generated DC with tolerogenic potential for prolongation of allograft survival. This minireview describes the development of a second-generation of DC-based strategies for transplantation tolerance based on the delivery in situ of donor allogeneic (allo)-Ag to quiescent DC of graft recipients by means of donor-derived apoptotic cells or exosomes. Donor leukocytes in early apoptosis are rich in allo-Ag, are internalized efficiently by recipient DC in vivo and deliver immunosuppressive signals to DC. Administration (i.v.) of donor apoptotic leukocytes prolongs bone marrow engraftment and cardiac allografts survival in mice by exerting a profound down-regulatory effect on the anti-donor T-cell response. Exosomes are nanovesicles (< 100 nm) produced by different cell types, including APC. DC-derived exosomes are rich in major histocompatibility complex (MHC) molecules that can be employed to target DC in situ. Once i.v. injected, exosomes carrying donor MHC molecules are captured by recipient's DC and prolong allograft survival in rodents. The use of the regulatory functions of apoptotic cells and exosomes may be useful tools to develop new strategies for transplantation tolerance.