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Double negative regulatory T cells in transplantation and autoimmunity: recent progress and future directions Free
Stephen C. Juvet 1,2 and Li Zhang2,3,4,*
1Division of Respirology and Clinician-Scientist Training Program, Department of Medicine, Institute of Medical Science, University of Toronto, Toronto, ON, Canada
2Toronto General Research Institute, University Health Network, Medical Discovery Tower, Room 2-807, 101 College Street, Toronto, ON, Canada
3Department of Immunology, University of Toronto, Toronto, ON, Canada
4Department of Laboratory Medicine and Pathobiology, University of Toronto and Toronto General Research Institute, University Health Network, Toronto, ON, Canada *Correspondence to:Li Zhang, E-mail: lzhang@uhnresearch.ca
J Mol Cell Biol, Volume 4, Issue 1, February 2012, 48-58,  https://doi.org/10.1093/jmcb/mjr043
Keyword: double-negative T cells, regulatory T cells, transplantation, autoimmunity, graft-versus-host disease, type 1 diabetes mellitus
T lymphocytes bearing the αβ T cell receptor (TCR) but lacking CD4, CD8, and markers of natural killer (NK) cell differentiation are known as ‘double-negative’ (DN) T cells and have been described in both humans and rodent models. We and others have shown that DN T cells can act as regulatory T cells (Tregs) that are able to prevent allograft rejection, graft-versus-host disease, and autoimmune diabetes. In the last few years, new data have revealed evidence of DN Treg function in vivo in rodents and humans. Moreover, significant advances have been made in the mechanisms by which DN Tregs target antigen-specific T cells. One major limitation of the field is the lack of a specific marker that can be used to distinguish truly regulatory DN T cells (DN Tregs) from non-regulatory ones, and this is the central challenge in the coming years. Here, we review recent progress on the role of DN Tregs in transplantation and autoimmunity, and their mechanisms of action. We also provide some perspectives on how DN Tregs compare with Foxp3+ Tregs.

Volume 4, Issue 1
February 2012