Safe Gene Therapy for Type 1 Diabetes
Abstract
Insulin expression was found in both lymph node (LN)-resident stromal cells of nonhemaetopoietic origin and bone marrow (BM)-derived antigen-presenting cells (APCs)1-3. Although little is known about the function of insulin expression in LNs, recent studies have shown that TSAexpressing stromal cells can effectively deplete TSA-specific autoreactive CD8+ T cells from the peripheral repertoire4-6. As for insulin expression in BM-derived APCs, discordant results have been reported regarding the specific cell subsets. Both (pro)insulin transcripts and proteins were found in human CD11c+ dendritic cells (DCs) in the thymus and the peripheral lymphoid tissues7. In contrast, Hansenne et al. found neither Ins1 nor Ins2 transcripts in mouse CD11chigh DCs, regardless of their maturation status8. Transplantation of BM cells harvested from NOD.Ins2+/+ mice failed to slow down diabetes progression in NOD.Ins2-/- recipients, suggesting that endogenous levels of Ins2 expression in BM-derived cells of NOD mice cannot restore peripheral tolerance to insulin9. However, these data should be interpreted with caution as the authors pointed out that the levels of Ins2-expression in spleen and pancreatic LN decrease significantly after weaning (3-4 weeks) in NOD mice10. The failure of restoring insulin tolerance might be attributed to the low levels of Ins2-expression in the transplanted BM cells. Thus, the role of insulin expression in secondary lymphoid tissues in regulating peripheral tolerance of beta-cells remains elusive.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2011
- Accession Number
- ADA553936
Entities
People
- Massimo Trucco
Organizations
- University of Pittsburgh