Regulatory T cells in kidney disease and transplantation.
Regulatory T cells (Tregs) have been shown to be important in maintaining immune homeostasis and preventing autoimmune disease, including autoimmune kidney disease. It is also likely that they play a role in limiting kidney transplant rejection and potentially in promoting transplant tolerance. Although other subsets of Tregs exist, the most potent and well-defined Tregs are the Foxp3 expressing CD4(+) Tregs derived from the thymus or generated peripherally. These CD4(+)Foxp3(+) Tregs limit autoimmune renal disease in animal models, especially chronic kidney disease, and kidney transplantation. Furthermore, other subsets of Tregs, including CD8 Tregs, may play a role in immunosuppression in kidney disease. The development and protective mechanisms of Tregs in kidney disease and kidney transplantation involve multiple mechanisms of suppression. Here we review the development and function of CD4(+)Foxp3(+) Tregs. We discuss the specific application of Tregs as a therapeutic strategy to prevent kidney disease and to limit kidney transplant rejection and detail clinical trials in this area of transplantation.
Centre for Transplantation and Renal Research, The Westmead Institute for Medical Research, University of Sydney, Westmead, New South Wales, Australia; Centre for Kidney Research, The Children's Hospital at Westmead, University of Sydney, Westmead, New South Wales, Australia.
Min
M
Hu
Centre for Kidney Research, The Children's Hospital at Westmead, University of Sydney, Westmead, New South Wales, Australia.
Yuan Min
YM
Wang
Centre for Transplantation and Renal Research, The Westmead Institute for Medical Research, University of Sydney, Westmead, New South Wales, Australia.
Yiping
Y
Wang
Centre for Kidney Research, The Children's Hospital at Westmead, University of Sydney, Westmead, New South Wales, Australia.
Geoff Y
GY
Zhang
Centre for Transplantation and Renal Research, The Westmead Institute for Medical Research, University of Sydney, Westmead, New South Wales, Australia.
Guoping
G
Zheng
Centre for Transplantation and Renal Research, The Westmead Institute for Medical Research, University of Sydney, Westmead, New South Wales, Australia.
Shounan
S
Yi
Centre for Transplantation and Renal Research, The Westmead Institute for Medical Research, University of Sydney, Westmead, New South Wales, Australia.
Philip J
PJ
O'Connell
Centre for Transplantation and Renal Research, The Westmead Institute for Medical Research, University of Sydney, Westmead, New South Wales, Australia.
David C H
DC
Harris
Centre for Kidney Research, The Children's Hospital at Westmead, University of Sydney, Westmead, New South Wales, Australia. Electronic address: stephen.alexander@health.nsw.gov.au.
Stephen I
SI
Alexander
D064591:Allografts / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology; D001706:Biopsy; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D007668:Kidney / Q000166:cytology / Q000276:immunology / Q000473:pathology; D007674:Kidney Diseases / Q000601:surgery*; D016030:Kidney Transplantation / Q000009:adverse effects*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D023001:Transplantation Tolerance / Q000276:immunology*
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007166:Immunosuppressive Agents
Foxp3; chronic kidney disease; regulatory T cells; transplantation