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Intravital imaging of CTLs killing islet cells in diabetic mice

Ken Coppieters UGent, Natalie Amirian and Matthias von Herrath (2012) JOURNAL OF CLINICAL INVESTIGATION. 122(1). p.119-131
abstract
Type 1 diabetes (T1D) is caused by autoimmune destruction of the insulin-producing beta cells in the pancreatic islets, which are essentially mini-organs embedded in exocrine tissue. CTLs are considered to have a predominant role in the autoimmune destruction underlying T1D. Visualization of CTL-mediated killing of beta cells would provide new insight into the pathogenesis of T1D, but has been technically challenging to achieve. Here, we report our use of intravital 2-photon imaging in mice to visualize the dynamic behavior of a virally expanded, diabetogenic CTL population in the pancreas at cellular resolution. Following vascular arrest and extravasation, CTLs adopted a random motility pattern throughout the compact exocrine tissue and displayed unimpeded yet nonlinear migration between anatomically nearby islets. Upon antigen encounter within islets, a confined motility pattern was acquired that allowed the CTLs to scan the target cell surface. A minority of infiltrating CTLs subsequently arrested at the beta cell junction, while duration of stable CTL-target cell contact was on the order of hours. Slow-rate killing occurred in the sustained local presence of substantial numbers of effector cells. Collectively, these data portray the kinetics of CTL homing to and between antigenic target sites as a stochastic process at the sub-organ level and argue against a dominant influence of chemotactic gradients.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
AUTOREACTIVE T-CELLS, GREEN FLUORESCENT PROTEIN, IN-VIVO, BETA-CELLS, ENTEROVIRUS INFECTION, PANCREATIC-ISLETS, VIRUS-INFECTION, DENDRITIC CELLS, TRANSGENIC MICE, 2-PHOTON MICROSCOPY
journal title
JOURNAL OF CLINICAL INVESTIGATION
J. Clin. Invest.
volume
122
issue
1
pages
119 - 131
Web of Science type
Article
Web of Science id
000298769400018
JCR category
MEDICINE, RESEARCH & EXPERIMENTAL
JCR impact factor
12.812 (2012)
JCR rank
4/119 (2012)
JCR quartile
1 (2012)
ISSN
0021-9738
DOI
10.1172/JCI59285
language
English
UGent publication?
no
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
2120305
handle
http://hdl.handle.net/1854/LU-2120305
date created
2012-05-30 10:01:14
date last changed
2012-06-07 13:11:43
@article{2120305,
  abstract     = {Type 1 diabetes (T1D) is caused by autoimmune destruction of the insulin-producing beta cells in the pancreatic islets, which are essentially mini-organs embedded in exocrine tissue. CTLs are considered to have a predominant role in the autoimmune destruction underlying T1D. Visualization of CTL-mediated killing of beta cells would provide new insight into the pathogenesis of T1D, but has been technically challenging to achieve. Here, we report our use of intravital 2-photon imaging in mice to visualize the dynamic behavior of a virally expanded, diabetogenic CTL population in the pancreas at cellular resolution. Following vascular arrest and extravasation, CTLs adopted a random motility pattern throughout the compact exocrine tissue and displayed unimpeded yet nonlinear migration between anatomically nearby islets. Upon antigen encounter within islets, a confined motility pattern was acquired that allowed the CTLs to scan the target cell surface. A minority of infiltrating CTLs subsequently arrested at the beta cell junction, while duration of stable CTL-target cell contact was on the order of hours. Slow-rate killing occurred in the sustained local presence of substantial numbers of effector cells. Collectively, these data portray the kinetics of CTL homing to and between antigenic target sites as a stochastic process at the sub-organ level and argue against a dominant influence of chemotactic gradients.},
  author       = {Coppieters, Ken and Amirian, Natalie and von Herrath, Matthias},
  issn         = {0021-9738},
  journal      = {JOURNAL OF CLINICAL INVESTIGATION},
  keyword      = {AUTOREACTIVE T-CELLS,GREEN FLUORESCENT PROTEIN,IN-VIVO,BETA-CELLS,ENTEROVIRUS INFECTION,PANCREATIC-ISLETS,VIRUS-INFECTION,DENDRITIC CELLS,TRANSGENIC MICE,2-PHOTON MICROSCOPY},
  language     = {eng},
  number       = {1},
  pages        = {119--131},
  title        = {Intravital imaging of CTLs killing islet cells in diabetic mice},
  url          = {http://dx.doi.org/10.1172/JCI59285},
  volume       = {122},
  year         = {2012},
}

Chicago
Coppieters, Ken, Natalie Amirian, and Matthias von Herrath. 2012. “Intravital Imaging of CTLs Killing Islet Cells in Diabetic Mice.” Journal of Clinical Investigation 122 (1): 119–131.
APA
Coppieters, K., Amirian, N., & von Herrath, M. (2012). Intravital imaging of CTLs killing islet cells in diabetic mice. JOURNAL OF CLINICAL INVESTIGATION, 122(1), 119–131.
Vancouver
1.
Coppieters K, Amirian N, von Herrath M. Intravital imaging of CTLs killing islet cells in diabetic mice. JOURNAL OF CLINICAL INVESTIGATION. 2012;122(1):119–31.
MLA
Coppieters, Ken, Natalie Amirian, and Matthias von Herrath. “Intravital Imaging of CTLs Killing Islet Cells in Diabetic Mice.” JOURNAL OF CLINICAL INVESTIGATION 122.1 (2012): 119–131. Print.