Intragraft FOXP3 protein or mRNA during acute renal allograft rejection correlates with inflammation, fibrosis, and poor renal outcome.
BACKGROUND
Forkhead box (FOXP3) is considered to be a specific marker for regulatory T cells. The aim of this study was to correlate intragraft FOXP3 at mRNA and cellular levels during renal allograft rejection to response to therapy and late clinical outcome.


METHODS
Immunostainings and quantitative reverse-transcriptase polymerase chain reaction for FOXP3, CD3, and transforming growth factor (TGF)-beta were performed and results were related to histopathologic and clinical outcome.


RESULTS
A good correlation between immunohistochemical analysis and mRNA levels for both CD3 and FOXP3 was observed. Intragraft FOXP3 was significantly related to tubulitis and interstitial fibrosis. A strong correlation was found between FOXP3 and CD3 mRNA and between FOXP3 and TGF-beta mRNA. No correlation was found between FOXP3 and response to therapy.


CONCLUSIONS
In conclusion, intragraft FOXP3 at both cellular and molecular levels parallels T-cell infiltration during acute rejection. FOXP3 does not predict response to antirejection therapy. FOXP3 correlates with renal fibrosis, TGF-beta, and poor late renal outcome.
Yapici
Unsal
U
Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Bemelman
Fréderike J
FJ
Scheepstra
Cornelis G
CG
Roelofs
Joris J T H
JJ
Claessen
Nike
N
van der Loos
Chris
C
van Donselaar-van der Pant
Karlijn
K
Bouts
Antonia H M
AH
Idu
Mirza M
MM
Rowshani
Ajda T
AT
ten Berge
Ineke J M
IJ
Florquin
Sandrine
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000235:genetics; D017252:CD3 Complex / Q000235:genetics; D002648:Child; D005260:Female; D005355:Fibrosis / Q000235:genetics / Q000503:physiopathology; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D006084:Graft Rejection / Q000453:epidemiology* / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000503:physiopathology; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D014019:Tissue Donors / Q000706:statistics & numerical data; D016212:Transforming Growth Factor beta / Q000235:genetics; D017211:Treatment Failure; D016896:Treatment Outcome; D055815:Young Adult
D015703:Antigens, CD; D017252:CD3 Complex; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta