title: Adoptive cell therapy using antigen-specific CD4⁻CD8⁻T regulatory cells to prevent autoimmune diabetes and promote islet allograft survival in NOD mice.
abstract: OBJECTIVE
  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
  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.
authors: Beijing Friendship Hospital, Capital Medical University, Beijing, People's Republic of China.
authors: D
authors: D
authors: Zhang
authors: W
authors: W
authors: Zhang
authors: T W
authors: TW
authors: Ng
authors: Y
authors: Y
authors: Wang
authors: Q
authors: Q
authors: Liu
authors: V
authors: V
authors: Gorantla
authors: F
authors: F
authors: Lakkis
authors: X X
authors: XX
authors: Zheng
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