101. FoxP3 cells and the pathophysiologic effects of brain death and warm ischemia in donor kidneys
- Author
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Annemiek M.A. Peeters, M. W.H.J. Demmers, Janneke N. Samsom, W. M. Mol, Ajda T. Rowshani, Jan N. M. IJzermans, Carla C. Baan, Willem Weimar, Karin Boer, Internal Medicine, Pediatrics, and Surgery
- Subjects
Male ,Pathology ,Time Factors ,CD3 Complex ,Epidemiology ,Biopsy ,Critical Care and Intensive Care Medicine ,Kidney ,T-Lymphocytes, Regulatory ,Living Donors ,Hepatitis A Virus Cellular Receptor 1 ,Warm Ischemia ,Kidney transplantation ,Cells, Cultured ,Membrane Glycoproteins ,Graft Survival ,Interleukin-17 ,FOXP3 ,Forkhead Transcription Factors ,Middle Aged ,Immunohistochemistry ,medicine.anatomical_structure ,Nephrology ,Creatinine ,Receptors, Virus ,Female ,Interleukin 17 ,medicine.symptom ,Inflammation Mediators ,Adult ,medicine.medical_specialty ,Brain Death ,Cold storage ,Inflammation ,Interferon-gamma ,Internal medicine ,medicine ,Humans ,Interleukin 8 ,RNA, Messenger ,Aged ,Transplantation ,business.industry ,Interleukin-8 ,Original Articles ,medicine.disease ,Kidney Transplantation ,Coculture Techniques ,Endocrinology ,Gene Expression Regulation ,Th17 Cells ,business ,Biomarkers - Abstract
Background and objectives 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 CD3e. 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.
- Published
- 2012