Table 3 Effect of neonatal tumor necrosis factor (TNF) and anti-TNF therapy on type 1 diabetes (T1DM) models

Model

Intervention

Result

Mechanism

1a.

T1DM in NOD mice

TNF, 1–2 μg i.p., q.o.d for 21 days from birth

Increased incidence and earlier onset of diabetes

? Further decrease in CD4⁺CD25⁺ regulatory T cells

? Decrease in thymic

T-cell-negative selection

1b.

T1DM in NOD mice

Anti-TNF, 20–100 μg i.p., q.o.d. for 21 days from birth

Complete, prolonged (1 year) absence of diabetes and islet cell autoimmunity

Dramatic increase in CD4⁺CD25⁺ regulatory T cells

[9, 10] (A Wu and HO McDevitt, unpublished observations)

? Increase in thymic

T-cell-negative selection

2.

T1DM in C57BL/6 mice expressing RIP-TNF

TNF overexpressed in β cells

Severe insulitis, but diabetes never occurs (unless transgenic RIP-B7.1 is introduced)

RIP-TNF appears to have induced a Th2 shift in islet-reactive T cells