Foxp3-transduced polyclonal regulatory T cells protect against chronic renal injury from adriamycin

• Published in: Journal of the American Society of Nephrology Vol. 17; no. 3; pp. 697 - 706
• Main Authors: YUAN MIN WANG, YU ZHANG, Geoff, YIPING WANG, MIN HU, HUILING WU, WATSON, Debbie, HORI, Shohei, ALEXANDER, Ian E, HARRIS, David C. H, ALEXANDER, Stephen I
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01-03-2006
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Applied cell therapy and gene therapy; Biological and medical sciences; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - physiology; Cell Proliferation - drug effects; Cells, Cultured; Disease Models, Animal; Doxorubicin; Flow Cytometry; Forkhead Transcription Factors - pharmacology; Immunohistochemistry; Kidney Failure, Chronic - chemically induced; Kidney Failure, Chronic - prevention & control; Male; Medical sciences; Mice; Mice, Inbred BALB C; Nephrology. Urinary tract diseases; Probability; Random Allocation; Reverse Transcriptase Polymerase Chain Reaction; Sensitivity and Specificity; T-Lymphocytes, Regulatory - drug effects; Transduction, Genetic; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Nephrology; Kidney traumatism; Doxorubicin; Urology; Prevention; Isomerases; Gene; T-Lymphocyte; Genetics; Regulatory cell; Transcription factor FOXP3; Kidney disease; DNA topoisomerase (ATP-hydrolysing); Urinary system disease; Enzyme; Rodentia; Enzyme inhibitor; Vertebrata; Antibiotic; Chronic; Mammalia; Mouse; Animal; Anthracyclins; Genetic engineering; Transduction; Gene therapy
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/ASN.2005090978

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.