Expression of regulatory T-cell-related molecule genes and clinical outcome in kidney transplant recipients.
BACKGROUND
Naturally occurring regulatory T cells have been associated with long-term allograft survival. We investigated whether gene transcripts of Treg-related molecules are upregulated or downregulated in kidney transplant recipients with different clinical outcomes and may serve as markers of operative tolerance.


METHODS
Expression levels of transcription factor (forkhead box P3 [FOXP3], t-bet, and GATA3), regulatory molecule (cytotoxic T-lymphocyte antigen-4, glucocorticoid-induced tumor necrosis factor receptor-related protein, tribbles protein-1, and transforming growth factor-beta), and chemokine receptor (CCR7 and CXCR4) genes were measured in kidney graft recipients with long-term (> or = 9 years) stable renal function (LTS) or chronic rejection (ChrRx). Patients on dialysis and healthy individuals served as controls.


RESULTS
The level of FOXP3 transcripts was lower in ChrRx patients than in LTS patients (P<0.01). The highest transforming growth factor-beta transcripts were observed in ChrRx and the highest CCR7 and CXCR4 transcripts were observed in LTS patients. In LTS patients, FOXP3 gene expression was associated with CXCR4 gene expression (P=0.015). FOXP3 and CCR7 transcript levels were higher in LTS patients without calcineurin inhibitor therapy than in LTS patients with calcineurin inhibitors.


CONCLUSIONS
Our results suggest that high expression of FOXP3 and chemokine receptor genes in LTS patients are possible indicators of a regulatory process that contributes to long-term allograft acceptance. Markers that were increased in LTS patients were found to be decreased in ChrRx patients, suggesting that rejection may partly be the result of a lack of this regulatory process. FOXP3 and CCR7 and CXCR4 transcripts might be used as markers to distinguish patients who developed long-term allograft acceptance from patients who are prone to ChrRx.
Alvarez
Cristiam M
CM
Grupo de Inmunología Celular e Inmunogenética, Facultad de Medicina, Instituto de Investigaciones Médicas, Universidad de Antioquia, Medellín Colombia.
Opelz
Gerhard
G
Garcia
Luis F
LF
Süsal
Caner
C
D000328:Adult; D000368:Aged; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D006085:Graft Survival / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000601:surgery / Q000628:therapy; D016030:Kidney Transplantation / Q000276:immunology* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D011184:Postoperative Period; D054387:Receptors, CXCR / Q000235:genetics; D019718:Receptors, CXCR4 / Q000235:genetics; D012016:Reference Values; D006435:Renal Dialysis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics; D014184:Transplantation, Homologous; D016896:Treatment Outcome
C501896:ACKR3 protein, human; C527276:CXCR4 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007166:Immunosuppressive Agents; D054387:Receptors, CXCR; D019718:Receptors, CXCR4; D016212:Transforming Growth Factor beta