Systemic NKT cell deficiency in NOD mice is not detected in peripheral blood: implications for human studies

SP Berzins, K Kyparissoudis, DG Pellicci… - Immunology and cell …, 2004 - Wiley Online Library
SP Berzins, K Kyparissoudis, DG Pellicci, KJ Hammond, S Sidobre, A Baxter, MJ Smyth
Immunology and cell biology, 2004Wiley Online Library
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 …
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.
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