Autoantigen-specific memory CD4+ T cells are prevalent early in progression to Type 1 diabetes

被引:33
作者
Oling, Viveka [1 ]
Reijonen, Helena [2 ]
Simell, Olli [3 ]
Knip, Mikael [4 ,5 ,6 ]
Ilonen, Jorma [1 ,7 ]
机构
[1] Univ Turku, Immunogenet Lab, FI-20520 Turku, Finland
[2] Virginia Mason, Benaroya Res Inst, Seattle, WA 98101 USA
[3] Univ Turku, Dept Pediat, FI-20521 Turku, Finland
[4] Univ Helsinki, Hosp Children & Adolescents, FI-00029 Helsinki, Finland
[5] Univ Helsinki, Folkhalsan Res Ctr, FI-00029 Helsinki, Finland
[6] Tampere Univ Hosp, Dept Pediat, FI-33521 Tampere, Finland
[7] Univ Eastern Finland, Dept Clin Microbiol, FI-70211 Kuopio, Finland
关键词
T1D; T cells; GAD65; Insulin; GLUTAMIC-ACID DECARBOXYLASE; CLASS-II TETRAMERS; AT-RISK SUBJECTS; PERIPHERAL-BLOOD; GENERAL-POPULATION; EPITOPES; INSULIN; AUTOANTIBODIES; PREDICTION; CHILDREN;
D O I
10.1016/j.cellimm.2011.12.008
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Autoreactive CD4(+) T cells contribute to the destruction of insulin producing beta cells in Type 1 diabetes (T1D). Using MHC class II tetramers, we have analyzed the frequency of GAD65-(274-286; 555-567) and insulin-(A1-15; A6-21) specific CD4(+)T cells in 31 children with T1D, 65 multiple autoantibody-positive children and 93 HLA- and age-matched controls. In a smaller group of children T-cell responses of memory origin to the same autoantigens were investigated. We observed a higher response to GAD65 555-567 in the autoantibody-positive children than in the controls (P = 0.017). Memory T-cell responses to GAD65 555-567 were more frequent among T1D patients (P = 0.025) and autoantibody-positive (P = 0.054), while all controls were negative (n = 28). In summary, the presence of antigen experienced GAD65-specific T cells in the subjects with diabetes-associated autoimmunity is encouraging for further directions in the prediction of T1D. (C) 2012 Elsevier Inc. All rights reserved.
引用
收藏
页码:133 / 139
页数:7
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