Induction of T regulatory cells attenuates idiopathic nephrotic syndrome.
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.
Le Berre
Ludmilla
L
INSERM U643, CHU Hôtel Dieu, 30 Bd Jean Monnet, 44093 Nantes, France.
Bruneau
Sarah
S
Naulet
Jeanne
J
Renaudin
Karine
K
Buzelin
Françoise
F
Usal
Claire
C
Smit
Helga
H
Condamine
Thomas
T
Soulillou
Jean-Paul
JP
Dantal
Jacques
J
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*
D000911:Antibodies, Monoclonal; D016207:Cytokines; D006146:Guanidines; D007166:Immunosuppressive Agents; C434185:LF 150195; D016328:NF-kappa B; D011948:Receptors, Antigen, T-Cell; C037258:gusperimus