Involvement of interleukin-2 and growth factors in chronic kidney allograft rejection in rats

Abstract

THE MOST IMPORTANT obstacle to organ transplantation today is the ill-defined process of chronic rejection. Chronically rejecting allografts are infiltrated with mononuclear cells, including T lymphocytes. As IL-2- and IL-2R-positive lymphocytes are constantly detected in chronically rejecting kidneys, they may determine the pace of chronic rejection.1 The development of interstitial fibrosis in chronic rejection has been attributed to local TGF-b and PDGF production.2 As it has been well described that cyclosporin A (CyA) induces TGF-b1 in vitro,3 we hypothesized that a suppression of the IL-2 pathway by this drug may be harmful over the long-term. To test this hypothesis, we studied how a continuous inhibition of the IL-2 pathway by either CyA or Tac interfered with the pace of chronic kidney allograft rejection in rats. We put a particular emphasis on their effects upon PDGF and TGF-b.