title: Dynamic changes in CD4+ CD25+(high) T cell apoptosis after the diagnosis of type 1 diabetes.
abstract: Because type 1 diabetes (T1D) is a chronic, autoimmune, T cell-mediated disease, interventions affecting T cells are expected to modulate the immune cascade and lead to disease remission. We propose that increased CD4(+) CD25(+high) T cell apoptosis, a trait we discovered in recent-onset T1D subjects, reflects T1D partial remission within the first 6 months after diagnosis. Apoptosis of forkhead box P3 (FoxP3)(+) CD4(+) CD25(+high) T cells, in addition to total daily doses of insulin (TDD), blood glucose, HbA1c and age, were measured in 45 subjects with T1D at various times after diagnosis. Sixteen healthy control subjects were also recruited to the study. Higher CD4(+) CD25(+high) T cell apoptosis levels were detected within the first 6 months of diagnosis (odds ratio = 1.39, P = 0.009), after adjustment for age, TDD and HbA1c. A proportional hazards model confirmed that the decline of apoptosis after diagnosis of T1D was related significantly to survival time (hazards ratio = 1.08, P = 0.014), with TDD and age also contributing to survival. During this time there was an inverse relationship between CD4(+) CD25(+high) T cell apoptosis with TDD (r = -0.39, P = 0.008). The CD4(+) CD25(+high) T cell apoptosis levels decline significantly after the first 6 months from diagnosis of T1D and may help in the close monitoring of autoimmunity. In parallel, there is an increase in TDD during this time. We also propose that CD4(+) CD25(+high) T cell apoptosis assay can be used to gauge the efficacy of the several immune tolerance induction protocols, now under way.
authors: The Max McGee National Center for Juvenile Diabetes and Human Molecular Genetics Center, Medical College of Wisconsin and the Children's Research Institute of the Children's Hospital of Wisconsin, WI 53226-0509, USA.
authors: S
authors: S
authors: Glisic-Milosavljevic
authors: T
authors: T
authors: Wang
authors: M
authors: M
authors: Koppen
authors: J
authors: J
authors: Kramer
authors: S
authors: S
authors: Ehlenbach
authors: J
authors: J
authors: Waukau
authors: P
authors: P
authors: Jailwala
authors: S
authors: S
authors: Jana
authors: R
authors: R
authors: Alemzadeh
authors: S
authors: S
authors: Ghosh
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000276:immunology*; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000008:administration & dosage; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood; D008297:Male; D012074:Remission Induction; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D006442:Glycated Hemoglobin; D007328:Insulin; D053645:Interleukin-2 Receptor alpha Subunit; C517652:hemoglobin A1c protein, human
references: J Immunol Methods. 2000 Oct 20;244(1-2):91-103
references: 11033022
references: Immunity. 2000 Apr;12(4):431-40
references: 10795741
references: J Immunol. 2002 Dec 1;169(11):6210-7
references: 12444126
references: Diabetes Care. 2003 Mar;26(3):662-7
references: 12610018
references: Immunol Rev. 2003 Feb;191:62-78
references: 12614352
references: BMJ. 2004 Mar 27;328(7442):750-4
references: 15044291
references: Pediatr Diabetes. 2004 Mar;5(1):16-9
references: 15043685
references: Curr Diab Rep. 2004 Aug;4(4):291-7
references: 15265472
references: Nat Rev Immunol. 2004 Aug;4(8):648-55
references: 15286731
references: Diabetes Care. 1987 Mar-Apr;10(2):164-9
references: 3556104
references: Diabetologia. 1987 Jul;30(7):453-9
references: 3311859
references: Acta Diabetol. 1998 Jul;35(2):91-5
references: 9747961
references: Arch Dis Child. 1999 Apr;80(4):367-9
references: 10086946
references: J Immunol. 2005 Apr 1;174(7):4081-9
references: 15778366
references: Diabetes Res Clin Pract. 2005 Jun;68(3):258-64
references: 15936469
references: Cell Prolif. 2005 Oct;38(5):301-11
references: 16202038
references: Diabetes Care. 2006 Jan;29 Suppl 1:S43-8
references: 16373932
references: Pediatr Diabetes. 2006 Apr;7(2):101-7
references: 16629716
references: Diabetes. 2006 Sep;55(9):2588-94
references: 16936208
references: Diabetes. 2006 Dec;55(12):3238-45
references: 17130466
references: PLoS One. 2007;2(1):e146
references: 17206281
references: J Pediatr Endocrinol Metab. 2001 Apr;14(4):435-41
references: 11327378