Selective intra-graft apoptosis and down-regulation of lymphocyte bcl-2, iNOs and CD95L expression in kidney-pancreas transplanted patients after anti-Thymoglobulin induction

Transpl Int. 2004 Nov;17(10):603-8. doi: 10.1007/s00147-004-0783-7. Epub 2004 Oct 29.

Abstract

Intra-graft infiltrating cells apoptosis was evaluated in 20 consecutive kidney-pancreas transplanted (KP) patients without kidney rejection. Two fine-needle aspirated biopsy (FNAB) and two peripheral blood lymphocytes (PBL) samples were obtained 14 days after transplantation. Immunosuppression was based on anti-Thymoglobulins (ATG) induction for 7 days and cyclosporine/mofetil mycophenolate as maintenance therapy. Ten matched healthy subjects were chosen as controls for PBL. Lymphocyte phenotypes and activation markers, apoptotic rate and lymphocyte expression of pro/anti-apoptotic molecules were analysed by flow cytometry analysis (FACS). Lymphocyte phenotypes and activation markers: higher levels of CD8 and CD4DR were evident in the graft (p < 0.05) than in PBL, CD3CD25 in PBL were higher in transplanted patients than in controls. Apoptotic rate and lymphocyte expression of pro- and anti-apoptotic molecules: a higher expression of annexin V, together with reduced lymphocytes CD95L, iNOs and Bcl-2 expression (PBL = 97.7+/-1.1% vs FNAB = 81.9+/-15.1%; p < 0.05) were evident in the graft than in PBL. In KP patients intra-graft apoptosis and reduced anti-apoptotic molecules were evident after ATG induction.

MeSH terms

  • Adult
  • Antilymphocyte Serum / therapeutic use*
  • Apoptosis*
  • Biomarkers / metabolism
  • Cyclosporine / therapeutic use
  • Down-Regulation
  • Fas Ligand Protein
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Kidney / physiopathology*
  • Kidney Transplantation*
  • Lymphocyte Activation
  • Lymphocytes / metabolism
  • Membrane Glycoproteins / metabolism
  • Mycophenolic Acid / analogs & derivatives*
  • Mycophenolic Acid / therapeutic use
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type II
  • Pancreas Transplantation*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism

Substances

  • Antilymphocyte Serum
  • Biomarkers
  • FASLG protein, human
  • Fas Ligand Protein
  • Immunosuppressive Agents
  • Membrane Glycoproteins
  • Proto-Oncogene Proteins c-bcl-2
  • Cyclosporine
  • NOS2 protein, human
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Mycophenolic Acid