Administration of recombinant human thioredoxin-1 significantly delays and prevents autoimmune diabetes in nonobese diabetic mice through modulation of autoimmunity.

BACKGROUND: Thioredoxin as a biological antioxidant plays an important role in regulating the redox system. The administration of recombinant thioredoxin has been demonstrated to be anti-inflammatory. In this study, the effect of recombinant human thioredoxin-1 (rhTrx-1) in preventing type 1 diabetes (T1D) in nonobese diabetic (NOD) mice was evaluated.
METHODS: Eight-week-old NOD mice were treated with intravenous injection of rhTrx-1 (5 µg/mouse/day) for 5 weeks (5 days a week), followed by every other day for additional 5 weeks. Diabetes onset was monitored twice a week. Pancreatic histology and β-cell mass were examined by hematoxylin and eosin (H&E) and insulin immunohistochemistry staining, respectively. Adoptive transfer experiments were executed to assess autoimmune T cells modulated by rhTrx treatment.
RESULTS: The intravenous administration of rhTrx-1 significantly delayed and prevented T1D in NOD mice. The histology data showed that rhTrx-1 treatment markedly reduced insulitic lesions and significantly preserved insulin-producing β cells. Adoptive transfer of spleen cells from rhTrx-1-treated mice into nonobese diabetic-severe combined immunodeficiency (NOD-SCID) mice significantly reduced the diabetes onset than transfer of those from phosphate-buffered saline-treated mice. Adoptive co-transfer experiments demonstrated that spleen cells from rhTrx-1-treated mice significantly delayed diabetes induced by the co-transferred diabetogenic spleen cells from the new-onset diabetic mice.
CONCLUSIONS: Antioxidant rhTrx-1 effectively prevents T1D which may be attributed to its activity to modulate autoimmunity.