Transplant International

, Volume 15, Issue 9, pp 446–454

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

Authors

  • Péter Hamar
    • Institute of Pathophysiology, Faculty of General Medicine, Semmelweis University, Nagyvárad tér 4, 1089 Budapest, Hungary
  • Attila Szabó
    • Department of Nephrology, University Hospital of Essen, Essen, Germany
  • Veronika Müller
    • Department of Nephrology, University Hospital of Essen, Essen, Germany
  • Uwe Heemann
    • Department of Nephrology, University Hospital of Essen, Essen, Germany
Original Article

DOI: 10.1007/s00147-002-0446-5

Cite this article as:
Hamar, P., Szabó, A., Müller, V. et al. Transpl Int (2002) 15: 446. doi:10.1007/s00147-002-0446-5

Abstract.

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 β (IL-2Rβ) mRNA synthesis were intense at 16 weeks and decreased thereafter. Unsurprisingly, both cyclosporin A and tacrolimus significantly inhibited IL-2 and IL-2Rβ 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)-β1 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-β1 mRNA returned to normal, while PDGF did not. Inhibition of T cells prevented the upregulation of TGF-β1 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.

Chronic allograft nephropathy T cells Interleukin-2 Transforming growth factor-β Platelet-derived growth factor

Copyright information

© Springer-Verlag 2002