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Demonstration of islet-autoreactive CD8 T cells in insulitic lesions from recent onset and long-term type 1 diabetes patients

Ken Coppieters UGent, Francesco Dotta, Natalie Amirian, Peter D Campbell, Thomas WH Kay, Mark A Atkinson, Bart O Roep and Matthias G von Herrath (2012) JOURNAL OF EXPERIMENTAL MEDICINE. 209(1). p.51-60
abstract
A direct association of islet-autoreactive T cells with. cell destruction in human pancreatic islets from type 1 diabetes (T1D) patients has never been demonstrated, and little is known about disease progression after diagnosis. Frozen pancreas samples were obtained from 45 cadaveric T1D donors with disease durations ranging from 1 wk to >50 yr, 14 nondiabetic controls, 5 nondiabetics with islet autoantibodies, 2 cases of gestational diabetes, and 6 T2D patients. Sections were systematically analyzed for the presence of insulin-sufficient beta cells, CD8(+) insulitic lesions, and HLA class I hyperexpression. Finally, consecutive sections from HLA-A2-expressing individuals were probed for CD8 T cell reactivity against six defined islet autoantigens associated with T1D by in situ tetramer staining. Both single and multiple CD8 T cell autoreactivities were detected within individual islets in a subset of patients up to 8 yr after clinical diagnosis. Pathological features such as HLA class I hyperexpression and insulitis were specific for T1D and persisted in a small portion of the patients with longstanding disease. Insulitic lesions consistently presented in a multifocal pattern with varying degrees of infiltration and. cell loss across affected organs. Our observations provide the first direct proof for islet autoreactivity within human islets and underscore the heterogeneous and chronic disease course.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
BETA-CELLS, PERIPHERAL-BLOOD, NOD MICE, MELLITUS, EPITOPE, ANTIGEN, TRANSPLANTATION, IDENTIFICATION, IMMUNOTHERAPY, PANCREAS
journal title
JOURNAL OF EXPERIMENTAL MEDICINE
J. Exp. Med.
volume
209
issue
1
pages
51 - 60
Web of Science type
Article
Web of Science id
000299820200006
JCR category
MEDICINE, RESEARCH & EXPERIMENTAL
JCR impact factor
13.214 (2012)
JCR rank
3/119 (2012)
JCR quartile
1 (2012)
ISSN
0022-1007
DOI
10.1084/jem.20111187
language
English
UGent publication?
no
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
2120313
handle
http://hdl.handle.net/1854/LU-2120313
date created
2012-05-30 10:01:14
date last changed
2012-06-08 09:22:14
@article{2120313,
  abstract     = {A direct association of islet-autoreactive T cells with. cell destruction in human pancreatic islets from type 1 diabetes (T1D) patients has never been demonstrated, and little is known about disease progression after diagnosis. Frozen pancreas samples were obtained from 45 cadaveric T1D donors with disease durations ranging from 1 wk to {\textrangle}50 yr, 14 nondiabetic controls, 5 nondiabetics with islet autoantibodies, 2 cases of gestational diabetes, and 6 T2D patients. Sections were systematically analyzed for the presence of insulin-sufficient beta cells, CD8(+) insulitic lesions, and HLA class I hyperexpression. Finally, consecutive sections from HLA-A2-expressing individuals were probed for CD8 T cell reactivity against six defined islet autoantigens associated with T1D by in situ tetramer staining. Both single and multiple CD8 T cell autoreactivities were detected within individual islets in a subset of patients up to 8 yr after clinical diagnosis. Pathological features such as HLA class I hyperexpression and insulitis were specific for T1D and persisted in a small portion of the patients with longstanding disease. Insulitic lesions consistently presented in a multifocal pattern with varying degrees of infiltration and. cell loss across affected organs. Our observations provide the first direct proof for islet autoreactivity within human islets and underscore the heterogeneous and chronic disease course.},
  author       = {Coppieters, Ken and Dotta, Francesco and Amirian, Natalie and Campbell, Peter D and Kay, Thomas WH and Atkinson, Mark A and Roep, Bart O and von Herrath, Matthias G},
  issn         = {0022-1007},
  journal      = {JOURNAL OF EXPERIMENTAL MEDICINE},
  keyword      = {BETA-CELLS,PERIPHERAL-BLOOD,NOD MICE,MELLITUS,EPITOPE,ANTIGEN,TRANSPLANTATION,IDENTIFICATION,IMMUNOTHERAPY,PANCREAS},
  language     = {eng},
  number       = {1},
  pages        = {51--60},
  title        = {Demonstration of islet-autoreactive CD8 T cells in insulitic lesions from recent onset and long-term type 1 diabetes patients},
  url          = {http://dx.doi.org/10.1084/jem.20111187},
  volume       = {209},
  year         = {2012},
}

Chicago
Coppieters, Ken, Francesco Dotta, Natalie Amirian, Peter D Campbell, Thomas WH Kay, Mark A Atkinson, Bart O Roep, and Matthias G von Herrath. 2012. “Demonstration of Islet-autoreactive CD8 T Cells in Insulitic Lesions from Recent Onset and Long-term Type 1 Diabetes Patients.” Journal of Experimental Medicine 209 (1): 51–60.
APA
Coppieters, K., Dotta, F., Amirian, N., Campbell, P. D., Kay, T. W., Atkinson, M. A., Roep, B. O., et al. (2012). Demonstration of islet-autoreactive CD8 T cells in insulitic lesions from recent onset and long-term type 1 diabetes patients. JOURNAL OF EXPERIMENTAL MEDICINE, 209(1), 51–60.
Vancouver
1.
Coppieters K, Dotta F, Amirian N, Campbell PD, Kay TW, Atkinson MA, et al. Demonstration of islet-autoreactive CD8 T cells in insulitic lesions from recent onset and long-term type 1 diabetes patients. JOURNAL OF EXPERIMENTAL MEDICINE. 2012;209(1):51–60.
MLA
Coppieters, Ken, Francesco Dotta, Natalie Amirian, et al. “Demonstration of Islet-autoreactive CD8 T Cells in Insulitic Lesions from Recent Onset and Long-term Type 1 Diabetes Patients.” JOURNAL OF EXPERIMENTAL MEDICINE 209.1 (2012): 51–60. Print.