AI Article Synopsis
- NKT cells play a crucial role in T cell development and immune responses through specific cytokines, and deficiencies in these cells are linked to the severity of Type 1 Diabetes Mellitus (T1DM).
- Administering antibodies to CD1d during early thymic development can increase the number of invariant NKT (iNKT) cells in NOD mice, while simultaneously inhibiting iNKT cell production in C57BL/6 mice.
- These findings suggest that targeting CD1d during development could help correct iNKT deficiencies in NOD mice, potentially inhibiting diabetes progression by enhancing TCR levels.
Article Abstract
Natural Killer T (NKT) cells can effect both T cell development and peripheral immune responses through T(H)1/T(H)2 cytokines. Some humans with Type 1 Diabetes Mellitus (T1DM) have numerical and functional NKT deficiencies that contribute to disease severity. Correcting these deficiencies inhibits diabetes in the non-obese diabetic (NOD) T1DM model, which shares similar deficiencies. Here we show that antibodies to CD1d, when given during early thymic development, induce specific increases in surface TCR of developing NOD and C57BL/6 CD4(+)CD8(+) (DP) invariant NKT (iNKT) cells. However, the addition of anti-CD1d causes distinct strain-specific population changes in response to treatment. These changes include: (1) a dose-dependent increase in NOD iNKT(TCR)(+) cells and, conversely, (2) an inhibition of B6 iNKT(TCR)(+) cell production. The observed NOD iNKT expansions correlated with diabetes inhibition in an in vitro T1DM system, suggesting that intrathymic anti-CD1d treatment may correct NOD numerical iNKT deficiencies through developmental TCR enhancement.
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