title: Heightened CD40 ligand gene expression in peripheral CD4+ T cells from patients with kidney allograft rejection.
abstract: BACKGROUND
  CD40 ligand (CD40L) gene expression is increased in rejecting allograft biopsies. We, therefore, tested the possibility that CD40L gene expression is heightened in peripheral CD4+ T cells during renal allograft rejection.
  
  
  METHODS
  CD40L gene expression in peripheral blood CD4+ T cells from two renal transplant groups was measured by quantitative reverse transcription-polymerase chain reaction (RT-PCR). Group 1: 20 patients with excellent renal transplant function; group 2: 25 patients with findings of acute and/or chronic allograft nephropathy (CAN); and group 3 of 12 normal controls. CD4+ cells were isolated by positive selection. The modifying effect of cyclosporine (CsA) and FK506 on CD40L gene expression was further tested in vitro in CD4+ T lymphocytes separated from pokeweed mitogen- (PWM) activated peripheral blood lymphocytes (PBL) preparations.
  
  
  RESULTS
  Mean+/-SD expressions of CD40L gene, in aM, in groups 1-3 were as follows: 0.0052+/-0.0094; 0.022+/-0.023 (P=0.0038 vs. group 2); and 0.014+/-0.005. Levels of CD40L gene expression correlated significantly with acute rejection Banff 97 score (R2=0.44, P=0.0004) and severity of intertubular capillary changes (ITCC) (R2=0.33, P=0.011). After in vitro activation, CD40L gene expression increased by approximately 4-fold and the addition of CsA or FK506 diminished CD40L gene expression to a base level.
  
  
  CONCLUSIONS
  Peripheral CD4+ T cell CD40L gene expression increases significantly in acute rejection and CAN and may serve as a non-invasive method to monitor allograft function and determine the biological response to CsA and FK506.
authors.affiliation: Department of Medicine, Royal University Hospital, Saskatoon, Saskatchewan, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Shoker
authors.forename: D
authors.initials: D
authors.lastname: George
authors.forename: H
authors.initials: H
authors.lastname: Yang
authors.forename: M
authors.initials: M
authors.lastname: Baltzan
mesh_terms: D000208:Acute Disease; D000328:Adult; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand; D016022:Case-Control Studies; D002908:Chronic Disease; D016572:Cyclosporine / Q000627:therapeutic use; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006084:Graft Rejection / Q000188:drug therapy / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D066298:In Vitro Techniques; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology* / Q000473:pathology; D008024:Ligands; D008562:Membrane Glycoproteins / Q000235:genetics*; D008875:Middle Aged; D016559:Tacrolimus / Q000627:therapeutic use
chemical_list: D019013:CD40 Antigens; D017931:DNA Primers; D007166:Immunosuppressive Agents; D008024:Ligands; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D016572:Cyclosporine; D016559:Tacrolimus