Insulin administration confers diabetes-preventive properties to NOD mice derived dendritic cells.
Administration of autoantigen can be of value for prevention of autoimmune diabetes and it has been speculated that the control point of dendritic cells (DC) for the induction of peripheral tolerance may be highly relevant. We examined the properties of DC associated with immune suppression in NOD mice by insulin injection subcutaneously and the ability of which to suppress diabetes transfer by diabetogenic effector cells in secondary NOD-SCID recipients. Our data showed that the surface expressions of MHC II and CD86 on NOD-derived DC were increased after insulin treatment compared with those on PBS controlled mice. The dendritic cells with a mature phenotype and increased MLR stimulation adoptively transferred immune tolerogenic effects in secondary NOD-SCID mice, which were associated with significant greater IL-10, TGF-beta production and CD4(+)CD25(+)T differentiation from splenocytes compared with NOD-SCID control recipients. Moreover, treatment with DC remarkably decreased the incidence of diabetes in secondary recipients. These results suggest that a subtype of DC generated by insulin subcutaneous treated NOD mice confers potential protection from diabetes through polarizing the immune response towards a Th2 regulatory pathway.
Xiang
Ming
M
Department of Pharmacology, School of Pharmacy, Tongji Medical College, HuaZhong Science and Technology University, Wuhan, People's Republic of China. xiangming@mails.tjmu.edu.cn
Zou
Xiaolei
X
Zhang
Chengliang
C
Zhao
Zengyu
Z
Xu
Jing
J
D000818:Animals; D001324:Autoantigens / Q000494:pharmacology; D001854:Bone Marrow Cells / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000187:drug effects*; D003922:Diabetes Mellitus, Type 1 / Q000517:prevention & control*; D005260:Female; D005434:Flow Cytometry; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D053645:Interleukin-2 Receptor alpha Subunit; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011236:Prediabetic State / Q000473:pathology / Q000517:prevention & control; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000502:physiology; D013778:Tetrazolium Salts; D013844:Thiazoles
D001324:Autoantigens; D016207:Cytokines; D007004:Hypoglycemic Agents; D007328:Insulin; D053645:Interleukin-2 Receptor alpha Subunit; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue