2012-09-01
FoxP3 T cells and the pathophysiologic effects of brain death and warm ischemia in donor kidneys
Publication
Publication
Clinical Journal of the American Society of Nephrology , Volume 7 - Issue 9 p. 1481- 1489
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 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.
Additional Metadata | |
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doi.org/10.2215/CJN.13041211, hdl.handle.net/1765/73402 | |
Clinical Journal of the American Society of Nephrology | |
Organisation | Department of Surgery |
Baan, C., Peeters, A., Demmers, M., Mol, W., Boer, K., Samsom, J., … Weimar, W. (2012). FoxP3 T cells and the pathophysiologic effects of brain death and warm ischemia in donor kidneys. Clinical Journal of the American Society of Nephrology, 7(9), 1481–1489. doi:10.2215/CJN.13041211 |