Foxp3-transduced polyclonal regulatory T cells protect against chronic renal injury from adriamycin.
Chronic proteinuric renal injury is a major cause of ESRD. Adriamycin nephropathy is a murine model of chronic proteinuric renal disease whereby chemical injury is followed by immune and structural changes that mimic human disease. Foxp3 is a gene that induces a regulatory T cell (Treg) phenotype. It was hypothesized that Foxp3-transduced Treg could protect against renal injury in Adriamycin nephropathy. CD4+ T cells were transduced with either a Foxp3-containing retrovirus or a control retrovirus. Foxp3-transduced T cells had a regulatory phenotype by functional and phenotypic assays. Adoptive transfer of Foxp3-transduced T cells protected against renal injury. Urinary protein excretion and serum creatinine were reduced (P<0.05), and there was significantly less glomerulosclerosis, tubular damage, and interstitial infiltrates (P<0.01). It is concluded that Foxp3-transduced Treg cells may have a therapeutic role in protecting against immune injury and disease progression in chronic proteinuric renal disease.
Centre for Kidney Research, Children's Hospital at Westmead, and Centre for Transplantation and Renal Research, University of Sydney at Westmead Millennium Institute, New South Wales 2145, Sydney, Australia.
Yuan Min
YM
Wang
Geoff Yu
GY
Zhang
Yiping
Y
Wang
Min
M
Hu
Huiling
H
Wu
Debbie
D
Watson
Shohei
S
Hori
Ian E
IE
Alexander
David C H
DC
Harris
Stephen I
SI
Alexander
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004317:Doxorubicin; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000494:pharmacology*; D007150:Immunohistochemistry; D007676:Kidney Failure, Chronic / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011336:Probability; D011897:Random Allocation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects*; D014161:Transduction, Genetic
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D004317:Doxorubicin