Systemic NKT cell deficiency in NOD mice is not detected in peripheral blood: implications for human studies.
In the diabetes-prone NOD mouse, there is a proven association between a systemic deficiency of NKT cells and the onset of type 1 diabetes. Numerous reports of similar defects within the NKT cell compartment of human type 1 diabetes patients suggested NKT cell levels might be a valuable predictor of susceptibility and could provide a target for therapeutic intervention. Two recent studies, however, found no association between type 1 diabetes and blood NKT cell levels in humans and consequently rejected a link between the onset of diabetes and NKT cell deficiency. This cast considerable doubts on the potential for NKT cell-based clinical applications and challenged the validity of the NOD mouse as a model of human type 1 diabetes. We now report that NKT cell levels in blood are a poor representation of those in other organs. Strikingly, systemic NKT cell deficiencies were identified in NOD mice with normal, or even raised, blood levels. This re-establishes the correlation between NKT cell deficiency and type 1 diabetes and raises important questions regarding the assaying of NKT cell levels in humans.
Berzins
Stuart P
SP
Department of Microbiology and Immunology, University of Melbourne, Royal Parade, Parkville, Victoria, Australia. berzins@unimelb.edu.au
Kyparissoudis
Kon
K
Pellicci
Daniel G
DG
Hammond
Kristen J
KJ
Sidobre
Stephane
S
Baxter
Alan
A
Smyth
Mark J
MJ
Kronenberg
Mitchell
M
Godfrey
Dale I
DI
D000818:Animals; D001769:Blood / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000473:pathology; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D009928:Organ Specificity / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*