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

From: Multiple roles for tumor necrosis factor-α and lymphotoxin α/β in immunity and autoimmunity

Model Intervention Result Mechanism References
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 Further decrease in CD4+CD25+ regulatory T cells [9, 10] (A Wu and HO McDevitt, unpublished observations)
    ? 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diabetes and islet cell autoimmunity Dramatic increase in CD4+CD25+ regulatory T cells [9, 10] (A Wu and HO McDevitt, unpublished observations)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 [11, 12]
  1. i.p., intraperitoneally; NOD, nonobese diabetic; q.o.d., every other day; RIP, rat insulin promoter; Th2, T helper cell type 2.