Natural killer cells distinguish innocuous and destructive forms of pancreatic islet autoimmunity.
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.
Poirot
Laurent
L
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
C
Mathis
Diane
D
D000818:Animals; D001327:Autoimmune Diseases / Q000150:complications / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D015415:Biomarkers / Q000032:analysis; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000276:immunology / Q000473:pathology; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007328:Insulin / Q000502:physiology; D007515:Islets of Langerhans / Q000276:immunology* / Q000473:pathology*; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018655:Lymphocyte Count; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD
D015415:Biomarkers; D007328:Insulin