T lymphocytes bearing the ab 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 m...T lymphocytes bearing the ab 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 Foxp31 Tregs.展开更多
基金Research in our laboratory has been supported by Canadian Institutes of Health Research Grant (#14431)Canadian Cancer Society to L.Z.S.C.J.received salary support from a Terry Fox Foundation/National Cancer Institute of Canada Clinical Research Fellowship (#18014)the Clinician-Scientist Training Program,Department of Medicine,University of Toronto.
文摘T lymphocytes bearing the ab 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 Foxp31 Tregs.
