Adoptive cell therapy using antigen-specific CD4-CD8- T regulatory cells to prevent autoimmune diabetes and promote islet allograft survival in NOD mice

D. Zhang, W. Zhang, T. W. Ng, Y. Wang, Q. Liu, V. Gorantla, F. Lakkis, X. X. Zheng

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Aims/hypothesis: A new differentiation pathway for CD4-CD8 - (DN) T cells has recently been identified that exhibits the potent function of peripheral converted DN T cells in suppressing immune responses and provides the potential to treat autoimmune diseases. The aim of this study was to determine if the DN T cells converted from CD4+ T cells of NOD mice retain the antigen-specific regulatory capacity and prevent autoimmune diabetes in vivo. We also sought to determine if the combination of DN T cells with rapamycin promotes islet allograft survival in autoimmune diabetic NOD recipients. Methods: NOD CD4+ T cells were converted to DN T cells in an in vitro mixed-lymphocyte reaction, with or without GAD65 peptide, as previously reported. The antigen-specific DN T cells were adoptively transferred to NOD/SCID mice, new-onset diabetic NOD mice or islet-allograft-recipient NOD mice as the part of cell-based therapy. The development of diabetes and allograft survival was assessed by monitoring blood glucose levels. Results: NOD CD4+ T cells were converted in vitro to DN T cells at a rate of 50% and expressed unique cell features. The DN T cells from NOD donors blocked autoimmunity and prevented diabetes in NOD models, and these effects were even greater for GAD65-peptide-primed DN T cells. DN T cells acted in conjunction with rapamycin to suppress alloantigen-triggered T cell proliferation, promoted apoptosis and prolonged islet allograft survival in NOD recipients. Conclusions/interpretation: Administration of the islet beta cell antigen-specific DN T cells can prevent the development of autoimmune diabetes and promote islet allograft survival in NOD mice.

Original languageEnglish
Pages (from-to)2082-2092
Number of pages11
JournalDiabetologia
Volume54
Issue number8
DOIs
StatePublished - Aug 2011
Externally publishedYes

Keywords

  • CD4CD8 regulatory T cells
  • Cell therapy
  • Islet transplantation
  • NOD mouse
  • Type 1 diabetes

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