Foxp3+ T cells in peripheral blood of renal transplant recipients and clinical correlations.
OBJECTIVE
Immunophenotype peripheral blood T cells from renal transplant recipients (RTR) using cellular markers of regulatory T cells (Tregs) and flow cytometry, including Foxp3, and correlate these findings with clinical parameters.


METHODS
Expression of phenotypic markers of Tregs was assessed by flow cytometric analysis of peripheral blood lymphocytes (PBL) from (i) RTR (n = 95); (ii) patients with end-stage renal failure (ESRF) awaiting transplantation (n = 17); and (iii) normal healthy controls (n = 18).


RESULTS
The percentage of CD4(+) CD25(+) Foxp3(+) cells within the CD4(+) cell population did not significantly alter at different time points post-transplant. However, the percentage of CD4(+) CD25(+) Foxp3(+) cells within the CD4(+) population was significantly lower in RTR compared with patients with ESRF. In contrast, RTR and ESRF had a similar percentage of CD4(+) CD25(+) cells expressing Foxp3. Multivariate analysis of PBL and clinical parameters demonstrated (i) a positive linear relationship between the percentage CD4(+) CD25(+) cells expressing Foxp3 and estimated glomerular filtration rate and (ii) a higher percentage of CD4(+) CD25(+) cells in the CD4(+) cell population in patients with malignancy (the majority were skin cancers). Malignancy also correlated strongly with time post-transplant and age of the RTR.


CONCLUSIONS
Immune monitoring of the PBL phenotype in RTR using CD4, CD25 and Foxp3 may stratify RTR and predict graft outcome and function, and risk of complications from immunosuppression. Longitudinal and functional studies of Tregs are essential to extend the findings of the present study.
Department of Surgery, The University of Melbourne, Austin Health/Northern Health, Heidelberg, Victoria, Australia.
Wen X
WX
Lin
Dale
D
Christiansen
Lu L
LL
Fu
Matthew A
MA
Roberts
Mauro S
MS
Sandrin
Francesco L
FL
Ierino
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000097:blood*; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival; D006801:Humans; D016130:Immunophenotyping / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood; D007676:Kidney Failure, Chronic / Q000097:blood / Q000276:immunology / Q000601:surgery*; D016030:Kidney Transplantation / Q000276:immunology*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015166:Monitoring, Immunologic; D015999:Multivariate Analysis; D009369:Neoplasms / Q000276:immunology; D018570:Risk Assessment; D012307:Risk Factors; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*; D013997:Time Factors; D016896:Treatment Outcome; D014739:Victoria; D014850:Waiting Lists
D015415:Biomarkers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit