FOXP3+ regulatory T-cells in renal allografts: correlation with long-term graft function and acute rejection.
BACKGROUND
The interpretation of a cellular infiltrate as cytotoxic or tolerogen represents an unsolved challenge in current transplantation. The so-called regulatory CD4+ CD25+ T-cells which express the FOXP3 gene have received increasing interest with respect to this question. The existing studies concerning the role of FOXP3+ Tregs for transplant tolerance yielded contradictory results.


METHODS
We examined the numbers of the FOXP3+ Tregs in two groups of renal allograft biopsies both showing cellular infiltration, but either without (n=29) or with signs of acute cellular rejection (n=26), by means of immunofluorescence and correlated the amount of FOXP3+ Tregs to renal function at the time of biopsy and after 1 and 2 years of follow up.


RESULTS
The number of FOXP3+ Tregs within infiltrates in non-rejecting biopsies did not correlate with renal function after 1 and 2 years. There were no significant differences in the numbers of FOXP3+ Tregs between biopsies with or without borderline infiltrates. Increased numbers of FOXP3+ Tregs were not associated with an ameliorated severity of graft rejection and did not correlate with outcome after the rejection episode and renal function after 1 and 2 years.


CONCLUSIONS
The identification of the FOXP3+ regulatory cells within the allograft cannot be considered as an appropriate marker for the interpretation of infiltrates as cytotoxic or tolerogenic or as a prognostic marker for later transplant function.
Department of Internal Medicine II, Institute of Pathology, School of Medicine, University Hospital Regensburg, Regensburg, Germany. dmitrij.kollins@klinik.uni-regensburg.de
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Kollins
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Stoelcker
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Hoffmann
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Bergler
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Reinhold
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Rümmele
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Farkas
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Krämer
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D000208:Acute Disease; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D018791:CD4 Lymphocyte Count; D003404:Creatinine / Q000097:blood; D005260:Female; D005455:Fluorescent Antibody Technique; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005858:Germany; D005919:Glomerular Filtration Rate; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival; D006801:Humans; D007668:Kidney / Q000276:immunology* / Q000503:physiopathology; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013997:Time Factors; D023001:Transplantation Tolerance; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D015415:Biomarkers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D003404:Creatinine