Long-term silencing of autoimmune diabetes and improved life expectancy by a soluble pHLA-DR4 chimera in a newly-humanized

Luis Pow Sang, Sai Majji, Sofia Casares, Teodor D. Brumeanu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Several human MHC class II (HLA) molecules are strongly associated with high incidence of autoimmune diseases including type 1 diabetes (T1D). The HLA-humanized mice may thus represent valuable tools to test HLA-based vaccines and therapeutics for human autoimmune diseases. Herein, we have tested the therapeutic potential of a soluble HLA-DR4-GAD65271-280 (hu DEF-GAD65) chimera of human use in a newly-generated NOD/DR4/B7 double transgenic (dTg) mouse that develops spontaneously an accelerated T1D regardless the gender. The NOD/DR4/B7 dTg mice generated by a two-step crossing protocol express the HLA-DR*0401 molecules on 20% of antigen presenting cells, the human B7 molecules in pancreas, and HLA-DR4/GAD65-specific T-cells in the blood. Some 75% of pre-diabetic NOD/DR4/B7 dTg mice treated with hu DEF-GAD65 chimera remained euglycemic and showed a stabilized pancreatic insulitis 6 months after treatment. The 25% non responders developing hyperglycemia survived 3-4 months longer than their untreated littermates. T1D prevention by this reagent occurred by a Th2/TR-1 polarization in the pancreas. This study strongly suggests that the use of soluble pHLA reagents to suppress/stabilize the T1D progression and to extend the life expectancy in the absence of side effects is an efficient and safe therapeutic approach.

Original languageEnglish
Pages (from-to)693-699
Number of pages7
JournalHuman Vaccines and Immunotherapeutics
Issue number3
StatePublished - Mar 2014
Externally publishedYes


  • HLA-humanized nod mouse
  • HLA-peptide chimera
  • T1d prevention and stabilization


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