title: Induction of T regulatory cells attenuates idiopathic nephrotic syndrome.
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.
authors.affiliation: INSERM U643, CHU Hôtel Dieu, 30 Bd Jean Monnet, 44093 Nantes, France.
authors.forename: Ludmilla
authors.initials: L
authors.lastname: Le Berre
authors.forename: Sarah
authors.initials: S
authors.lastname: Bruneau
authors.forename: Jeanne
authors.initials: J
authors.lastname: Naulet
authors.forename: Karine
authors.initials: K
authors.lastname: Renaudin
authors.forename: Françoise
authors.initials: F
authors.lastname: Buzelin
authors.forename: Claire
authors.initials: C
authors.lastname: Usal
authors.forename: Helga
authors.initials: H
authors.lastname: Smit
authors.forename: Thomas
authors.initials: T
authors.lastname: Condamine
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Soulillou
authors.forename: Jacques
authors.initials: J
authors.lastname: Dantal
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D016207:Cytokines / Q000235:genetics; D005923:Glomerulosclerosis, Focal Segmental / Q000188:drug therapy / Q000276:immunology; D006146:Guanidines / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D016328:NF-kappa B / Q000502:physiology; D009404:Nephrotic Syndrome / Q000188:drug therapy* / Q000276:immunology; D051381:Rats; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D012008:Recurrence; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D016207:Cytokines; D006146:Guanidines; D007166:Immunosuppressive Agents; C434185:LF 150195; D016328:NF-kappa B; D011948:Receptors, Antigen, T-Cell; C037258:gusperimus