Cutting edge: interactions through the IL-10 receptor regulate autoimmune diabetes.
BDC2.5/nonobese diabetic (NOD) transgenic mice express a TCR from a diabetogenic T cell clone yet do not spontaneously develop diabetes at high incidence. Evidence exists showing that in the absence of endogenous TCR alpha-chain rearrangements this transgenic mouse spontaneously develops diabetes and that CTLA-4 negatively regulates diabetes onset. This strongly suggests that onset of diabetes in BDC2.5/NOD mice is governed by T cell regulation. We addressed the mechanism of immune regulation in BDC2.5/NOD mice. We find that activated spleen cells from young, but not old, BDC2.5/NOD mice are able to transfer diabetes to NOD-scid recipients. We have used anti-IL-10R to show that the failure of splenocytes from older mice to transfer diabetes is due to dominant regulation. We furthermore found that diabetes developed following anti-IL-10R treatment of 6-wk old BDC2.5/NOD mice indicating that endogenous IL-10 plays a key role in the regulation of diabetes onset in this transgenic mouse.
Phillips
J M
JM
Department of Pathology, University of Cambridge, Cambridge, United Kingdom.
Parish
N M
NM
Drage
M
M
Cooke
A
A
D019264:Adoptive Transfer; D000375:Aging / Q000235:genetics / Q000276:immunology; D000818:Animals; D000918:Antibody Specificity / Q000235:genetics; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D005260:Female; D007106:Immune Sera / Q000502:physiology; D016753:Interleukin-10 / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000235:genetics; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D018123:Receptors, Interleukin / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D053701:Receptors, Interleukin-10; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology / Q000637:transplantation
D016207:Cytokines; D007106:Immune Sera; D011948:Receptors, Antigen, T-Cell; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D015375:Receptors, Interleukin-2; D016753:Interleukin-10