Heightened CD40 ligand gene expression in peripheral CD4+ T cells from patients with kidney allograft rejection.
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.
Shoker
A
A
Department of Medicine, Royal University Hospital, Saskatoon, Saskatchewan, Canada.
George
D
D
Yang
H
H
Baltzan
M
M
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
D019013:CD40 Antigens; D017931:DNA Primers; D007166:Immunosuppressive Agents; D008024:Ligands; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D016572:Cyclosporine; D016559:Tacrolimus