CD4+CD25+ regulatory T cells control the progression from periinsulitis to destructive insulitis in murine autoimmune diabetes.
Non-obese diabetic (NOD) mice develop spontaneous T-cell responses against pancreatic beta-cells, leading to islet cell destruction and diabetes. Despite high genetic similarity, non-obese resistant (NOR) mice do not develop diabetes. We show here that spleen cells of both NOD and NOR mice respond to the islet cell antigen glutamic acid decarboxylase-65 in IFN-gamma-ELISPOT assays. Moreover, NOR-T cells induce periinsulitis in NOD SCID recipient mice. Thus, a potentially pathogenic islet cell-specific T-cell response arises in NOR and NOD mice alike; the mechanism that prevents the autoimmune progression of self-reactive T cells in NOR mice presumably acts at the level of effector function. Consistent with this hypothesis, CD4+CD25+ cell-depleted spleen cells from NOR mice mediated islet cell destruction and overt diabetes in NOD SCID mice. Therefore, islet cell-specific effector cells in NOR mice appear to be under the control of CD4+CD25+ regulatory T cells, confirming the importance of regulatory cells in the control of autoimmune diabetes.
Ott
Patrick A
PA
Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Anderson
Michael R
MR
Tary-Lehmann
Magdalena
M
Lehmann
Paul V
PV
D019264:Adoptive Transfer; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000276:immunology* / Q000473:pathology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D018398:Homeodomain Proteins / Q000235:genetics; D007515:Islets of Langerhans / Q000276:immunology* / Q000473:pathology*; D007527:Isoenzymes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D010455:Peptides / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
D018398:Homeodomain Proteins; D007527:Isoenzymes; D010455:Peptides; D015375:Receptors, Interleukin-2; C064658:RAG-1 protein; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2