Treatment of diabetes in NOD mice by gene transfer of Ig-fusion proteins into B cells: Role of T regulatory cells

Nadejda Soukhareva, Yufei Jiang, David W. Scott*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


We previously reported that retrovirally mediated gene expression of Ig fusion proteins leads to specific immunologic tolerance and successful treatment of autoimmune conditions. Thus, a single dose of GAD65-IgG- or (Pro) Insulin-IgG-transduced B cells delays the onset and decreases the incidence of diabetes in young (7-12 weeks old) NOD female mice. Herein, we tested the role of regulatory T cells by in vivo treatment with anti-CD25 before B-cell gene therapy or by in vitro ablation of CD25+ cells from tolerized hosts in an adoptive transfer model. Our results demonstrate that anti-CD25 treatment, like cyclophosphamide, partially blocks the efficacy of gene therapy for tolerance. Moreover, B-cell therapy is effective at preventing diabetes transfer by female T cells (from older diabetic mice) into intact male recipients with normal islets, but failed to do so in NOD-scid recipients. This is due in part to homeostatic proliferation but also to the absence of CD25+ T cells in the latter hosts. Tolerance induced in younger NOD females can be stably transferred to NOD-scid recipients. However, physical removal of CD25+ cells abrogates the transfer of tolerance. Therefore, we conclude that CD4+, CD25+ regulatory T cells are required for the induction as well as maintenance of tolerance in this gene therapy model. The phenotype of these induced regulatory T cells is under investigation.

Original languageEnglish
Pages (from-to)41-46
Number of pages6
JournalCellular Immunology
Issue number1
StatePublished - Mar 2006
Externally publishedYes


  • Diabetes
  • Gene therapy
  • IgG fusion protein
  • Regulatory T cells
  • Tolerance


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