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The involvement of activated T cells and growth-factor production in the early and late phase of chronic kidney allograft nephropathy in rats.

  • Metaadatok
Tartalom: http://www.springerlink.com/content/fe0b7g761ejyqltp/
Archívum: MTA Könyvtár
Gyűjtemény: Status = Published


Type = Article
Cím:
The involvement of activated T cells and growth-factor production in the early and late phase of chronic kidney allograft nephropathy in rats.
Létrehozó:
Hamar, Péter
Szabó, Attila József
Müller, Veronika
Heemann, Uwe
Kiadó:
Springer & Wiley-Blackwell
Dátum:
2002-10
Téma:
QR180 Immunology / immunológia
RJ Pediatrics / gyermekgyógyászat
Tartalmi leírás:
T cells are thought to play a regulatory role in chronic allograft nephropathy (CAN). Thus, we investigated whether lymphocyte inhibition influences CAN. Fisher rat (F-344) kidneys were transplanted orthotopically into Lewis rats. Animals received cyclosporin A (1.5 mg/kg per day, s.c.) for 10 days and were treated daily with either cyclosporin A (1.5 mg/kg), tacrolimus (0.16 mg/kg), or a vehicle thereafter ( n=15 per group). Kidneys were harvested at 16 or 24 weeks. Interleukin-2 (IL-2) and interleukin-2 receptor beta (IL-2Rbeta) mRNA synthesis were intense at 16 weeks and decreased thereafter. Unsurprisingly, both cyclosporin A and tacrolimus significantly inhibited IL-2 and IL-2Rbeta at both time points. Proteinuria increased more rapidly in controls than in treated animals. Morphologically, over 40% of glomeruli were sclerosed by 16 weeks in controls, and ED-1+ macrophages and CD5+ T cells infiltrated the graft. IL-2 mRNA synthesis paralleled the number of infiltrating cells. Inhibition of T-cell proliferation significantly reduced glomerulosclerosis and leukocyte infiltration at both time points. Transforming growth factor (TGF)-beta(1) and platelet-derived growth factor (PDGF) synthesis were highly upregulated in controls at 16 weeks, the time of peak infiltration. At 24 weeks, as cellular infiltration was replaced by scar formation, TGF-beta(1) mRNA returned to normal, while PDGF did not. Inhibition of T cells prevented the upregulation of TGF-beta(1) at both time points; however, PDGF was suppressed only at week 16. These results indicate a beneficial effect of continuous suppression of T cells in CAN. T cells are probably more important in the early, inflammatory phase.
Típus:
Article
PeerReviewed
Formátum:
application/pdf
Azonosító:
Hamar, Péter and Szabó, Attila József and Müller, Veronika and Heemann, Uwe (2002) The involvement of activated T cells and growth-factor production in the early and late phase of chronic kidney allograft nephropathy in rats. Transplant international : official journal of the European Society for Organ Transplantation, 15 (9-10). pp. 446-54. ISSN 0934-0874
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