Experimental extracorporeal photopheresis therapy significantly delays the development of diabetes in non-obese diabetic mice.
In our previous studies, we demonstrated that infusion of apoptotic cells significantly prevented type 1 diabetes (T1D) in non-obese diabetic (NOD) mice. Extracorporeal photopheresis (ECP) is an apoptotic cell-based therapy used clinically for immune-mediated disorders. In this study, we examined the effect that intravenous delivery of apoptotic cells (ECP-treated) has in the prevention of T1D in NOD mice. We discovered that five weekly injections of ECP-treated NOD spleen cells, beginning at 8 weeks of age, significantly delayed diabetes onset. Furthermore, cell dose studies demonstrated that low dose ECP-treated spleen cells (2x10(5) cells/injection/mouse) had similar protective effects as compared to high dose (5x10(6) cells/injection). In contrast to ECP-treated cells alone, ECP-treated cells combined with beta cell antigens appeared to improve the protective effect as shown by the marked reduction in insulitis in the islets. Delivery of ECP-treated spleen cells or ECP-treated spleen cells plus beta cell antigen increased Foxp3(+) Tregs, and beta cell antigen-specific T cell proliferation was significantly suppressed in vivo in these two groups. In addition, we found that ECP-treated cells did not induce global immunosuppression or autoimmunity against nuclear antigens. In conclusion, ECP-treated cells provide a safe and effective approach in T1D prevention, suggesting that clinical ECP has great potential for managing human T1D.
Xia
Chang-Qing
CQ
Department of Pathology, Immunology and Laboratory Medicine, University of Florida, Gainesville, FL 32610, USA. xia@pathology.ufl.edu
Chernatynskaya
Anna
A
Lai
Yimu
Y
Campbell
Kim A
KA
Clare-Salzler
Michael J
MJ
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001773:Blood Cells / Q000276:immunology / Q000637:transplantation*; D002469:Cell Separation; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000628:therapy*; D005260:Female; D005434:Flow Cytometry; D051379:Mice; D016688:Mice, Inbred NOD; D017893:Photopheresis / Q000379:methods*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology