Altered natural killer cells in type 1 diabetic patients.
Evidence from animal models suggests that natural killer (NK) cells can be important players in the development of type 1 diabetes, although data in humans are still sparse. We studied the frequency and activation state of blood NK cells at different stages of human type 1 diabetes, and whether genetic or phenotypic NK cell peculiarities could be associated with an early onset of diabetes. The onset period is marked by a slight reduction in blood NK cells, but these are unusually activated in some patients (gamma-interferon expression). This activation status does not correlate, however, with a particularly young age at onset. In contrast, NK cells in patients with long-standing type 1 diabetes had a markedly lower expression of p30/p46 NK-activating receptor molecules compared with those of control subjects. A slightly decreased expression of NKG2D in all type 1 diabetic patients relative to control subjects was observed, independent of the duration of disease, parallel to prior observations in the NOD mouse. Finally, type 1 diabetic patients had an increased frequency of KIR gene haplotypes that include the activating KIR2DS3 gene, with a genetic interaction between the KIR and HLA complexes. The reduced activation of NK cells in individuals with long-standing type 1 diabetes would seem to be a consequence rather than a cause, but other peculiarities may relate to type 1 diabetes pathogenesis.
Rodacki
Melanie
M
Joslin Diabetes Center, Boston, MA, USA.
Svoren
Britta
B
Butty
Vincent
V
Besse
Whitney
W
Laffel
Lori
L
Benoist
Christophe
C
Mathis
Diane
D
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000276:immunology*; D003928:Diabetic Nephropathies / Q000276:immunology; D018450:Disease Progression; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics; D007694:Killer Cells, Natural / Q000276:immunology*; D050177:Overweight; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger; D007371:Interferon-gamma