Induction of T Regulatory Cells Attenuates Idiopathic Nephrotic Syndrome
Open Access
- 1 January 2009
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Journal of the American Society of Nephrology
- Vol. 20 (1), 57-67
- https://doi.org/10.1681/asn.2007111244
Abstract
Buffalo/Mna rats spontaneously develop FSGS and nephrotic syndrome as a result of an immune disorder. Similar to some humans with FSGS, the disease recurs after renal transplantation, suggesting the involvement of a circulating factor. Here, we tested the effect of several immunosuppressive treatments on these rats. Although corticosteroids, cyclosporin A, and anti–T cell receptor treatment reduced proteinuria, only the deoxyspergualin derivative LF15-0195 led to a rapid and complete normalization of proteinuria. Furthermore, this compound led to the regression of renal lesions during both the initial disease and posttransplantation recurrence. The frequency of splenic and peripheral CD4+CD25+FoxP3+ T lymphocytes significantly increased with remission. Moreover, the transfer of purified LF15-0195–induced CD4+CD25+ T cells to irradiated Buff/Mna rats significantly reduced their proteinuria compared with the transfer of untreated control cells, suggesting that LF15-0195 induces regulatory T cells that are able to induce regression of rat nephropathy. These data suggest that idiopathic nephrotic syndrome/FSGS disease can be regulated by cellular transfer, but how this regulation leads to the reorganization of the podocyte cytoskeleton remains to be determined.Keywords
This publication has 51 references indexed in Scilit:
- DnIKK2-Transfected Dendritic Cells Induce a Novel Population of Inducible Nitric Oxide Synthase???Expressing CD4+CD25??? Cells with Tolerogenic PropertiesTransplantation, 2007
- LF 15-0195 immunosuppressive agent enhances activation-induced T-cell death by facilitating caspase-8 and caspase-10 activation at the DISC levelBlood, 2003
- Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT MethodMethods, 2001
- LF15-0195 prevents the induction and inhibits the progression of rat anti-GBM diseaseKidney International, 2001
- A new method of measuring albumin permeability in isolated glomeruliKidney International, 1996
- 15‐Deoxyspergualin: A Newly Developed Immunosuppressive Agent and Its Mechanism of Action and Clinical Effect: A ReviewArtificial Organs, 1996
- INDUCTION OF SPECIFIC UNRESPONSIVENESS TO CARDIAC ALLOGRAFTS BY SHORT-TERM ADMINISTRATION OF ANTI T CELL RECEPTOR αβ ANTIBODY1Transplantation, 1994
- New rapid technique for renal transplantation in the ratMicrosurgery, 1992
- Decrease of mononuclear phagocyte cell functions and prolongation of graft survival in experimental transplantation by (±)-15-deoxyspergualinInternational Journal of Immunopharmacology, 1987
- DEVELOPMENT OF HYPERTENSION AND PROTEINURIA WITH AGE IN FAWN-HOODED RATSClinical and Experimental Pharmacology and Physiology, 1986