title: FoxP3 T cells and the pathophysiologic effects of brain death and warm ischemia in donor kidneys.
abstract: OBJECTIVE
  Forkhead box P3 regulatory T cells control inflammatory responses, but it remains unclear whether they inhibit brain death-initiated inflammation and tissue injury in deceased kidney donors.   DESIGN, SETTING, PARTICIPANTS,  MEASUREMENT:  To study the actions of regulatory T cells at various stages of the donation and transplantation procedure, forkhead box P3, regulatory and inflammatory cytokine expression, and tissue injury markers were determined in time 0 kidney biopsies from deceased and living donors. Additionally, the interaction between forkhead box P3+ T cells and kidney injury molecule-1 by activated primary tubular epithelial cells was studied.
  
  
  RESULTS
  After cold storage, the deceased donor kidneys expressed the higher mRNA levels of kidney injury molecule-1 and CD3ε. In these samples, the inflammatory cytokines IL-8 and IFN-γ and markers associated with regulation (forkhead box P3, TGF-β, and IL-10) were highly expressed compared with living donor kidneys. Correlations were found between mRNA expression levels of forkhead box P3 and kidney injury molecule-1 and forkhead box P3 and IFN-γ. Immunohistochemical analysis confirmed the presence of forkhead box P3+ T cells in donor kidneys. Renal function (analyzed by serum creatinine levels) at the first week posttransplantation correlated with kidney injury molecule-1 and forkhead box P3 mRNA levels. In vitro studies showed that kidney injury molecule-1 expression by primary tubular epithelial cells was 63% (mean) lower when cocultured with regulatory T cells compared with control T cells.
  
  
  CONCLUSIONS
  These results show that donor forkhead box P3+ T cells infiltrate the deceased donor kidney, where they may control inflammatory and injury responses.
authors: Department of Internal Medicine, Erasmus Medical Center, University Medical Center, Rotterdam, The Netherlands. c.c.baan@erasmusmc.nl
authors: Carla C
authors: CC
authors: Baan
authors: Annemiek M A
authors: AM
authors: Peeters
authors: Martijn W H J
authors: MW
authors: Demmers
authors: Wendy M
authors: WM
authors: Mol
authors: Karin
authors: K
authors: Boer
authors: Janneke N
authors: JN
authors: Samsom
authors: Ajda T
authors: AT
authors: Rowshani
authors: Jan N M
authors: JN
authors: Ijzermans
authors: Willem
authors: W
authors: Weimar
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001706:Biopsy; D001926:Brain Death / Q000276:immunology* / Q000503:physiopathology; D017252:CD3 Complex / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D003404:Creatinine / Q000097:blood; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005786:Gene Expression Regulation; D006085:Graft Survival; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007668:Kidney / Q000276:immunology / Q000378:metabolism / Q000601:surgery*; D016030:Kidney Transplantation / Q000276:immunology*; D019520:Living Donors; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D052096:Warm Ischemia / Q000009:adverse effects
chemical_list: D015415:Biomarkers; D017252:CD3 Complex; C115335:CD3E protein, human; C508606:CXCL8 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D018836:Inflammation Mediators; D020381:Interleukin-17; D016209:Interleukin-8; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011991:Receptors, Virus; D007371:Interferon-gamma; D003404:Creatinine