Extracorporeal photopheresis-induced immune tolerance: a focus on modulation of antigen-presenting cells and induction of regulatory T cells by apoptotic cells.
OBJECTIVE
This review is intended to introduce recent advances in the research surrounding extracorporeal photopheresis (ECP) with a focus on how apoptotic cells modulate antigen-presenting cells and induce regulatory T cells, given that ECP therapy induces apoptosis of leukocytes collected through leukapheresis.


RESULTS
It has been suggested that ECP therapy, unlike other immunosuppressive regimens, does not cause global immunosuppression, but induces immune tolerance. Recent clinical and animal studies demonstrate that ECP therapy induces antigen-specific regulatory T cells, including CD4+CD25+FoxP3+ T cells and IL-10-producing Tr1 cells, that may arise secondarily to the induction of tolerogenic antigen-presenting cells (APCs) by infusion of apoptotic cells. It has also been suggested that ECP therapy may induce IL-10-producing regulatory B cells and regulatory CD8+ T cells. Finally, several recent studies, which examined the cellular elements involved in the uptake of apoptotic cells, demonstrated that apoptotic cells modulate APCs through binding to specific receptors, particularly TAM receptors that provide inhibitory signals that block APC activation.


CONCLUSIONS
ECP therapy induces immune tolerance through modulation of antigen-presenting cells as well as induction of regulatory T cells. ECP therapy has great potential in the management of allogeneic transplantation and autoimmune diseases.
Xia
Chang-Qing
CQ
Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, Florida 32610, USA.
Campbell
Kim A
KA
Clare-Salzler
Michael J
MJ
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D017209:Apoptosis; D002454:Cell Differentiation; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D016753:Interleukin-10 / Q000378:metabolism; D016377:Organ Transplantation; D017893:Photopheresis; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D023001:Transplantation Tolerance
D016753:Interleukin-10; D020794:Receptor Protein-Tyrosine Kinases