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PMID: 15141080 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Natural killer cells distinguish innocuous and destructive forms of pancreatic islet autoimmunity.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 101 ·No. 21 ·2004-05-25 ·Pages 8102-7

Poirot L, Benoist C, Mathis D

Abstract

In both human patients and murine models, the progression from insulitis to diabetes is neither immediate nor inevitable, as illustrated by the innocuous versus destructive infiltrates of BDC2.5 transgenic mice on the nonobese diabetic (NOD) versus C57BL/6.H-2g7 genetic backgrounds. Natural killer (NK)-cell-specific transcripts and the proportion of NK cells were increased in leukocytes from the aggressive BDC2.5/B6.H-2g7 lesions. NK cell participation was also enhanced in the aggressive lesions provoked by CTLA-4 blockade in BDC2.5/NOD mice. In this context, depletion of NK cells significantly inhibited diabetes development. NOD and B6.H-2g7 mice exhibit extensive variation in NK receptor expression, reminiscent of analogous human molecules. NK cells can be important players in type 1 diabetes, a role that was previously underappreciated.

MeSH Terms
Animals Autoimmune Diseases/complications,genetics,immunology,pathology Biomarkers/analysis Diabetes Complications Diabetes Mellitus/immunology,pathology Gene Expression Profiling Humans Inflammation/complications,genetics,immunology,pathology Insulin/physiology Islets of Langerhans/immunology,pathology Killer Cells, Natural/cytology,immunology,metabolism Lymphocyte Count Mice Mice, Inbred C57BL Mice, Inbred NOD
Chemicals
Biomarkers Insulin
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Poirot Laurent
Section on Immunology and Immunogenetics, Joslin Diabetes Center, and Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, One Joslin Place, Boston, MA 02215, USA.
Benoist Christophe
Mathis Diane
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0402065101
Published
2004-05-25
Epub
2004-00-12
Pages
8102-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC419564
Subset
IM
Grants
NIAID NIH HHS · P01 AI54904-01 · United States
NIDDK NIH HHS · 2 P30 DK36836-17 · United States
NIAID NIH HHS · P01 AI054904 · United States
NIDDK NIH HHS · P30 DK036836 · United States
NIAID NIH HHS · P01 AI039671 · United States
NIAID NIH HHS · P01 AI39671-08 · United States
External Links
PubMed source DOI: 10.1073/pnas.0402065101 PMC Full Text View journal details
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