Department of Internal Medicine, Erasmus Medical Center, University Medical Center, Rotterdam, The Netherlands.
Clin J Am Soc Nephrol. 2012 Sep;7(9):1481-9. doi: 10.2215/CJN.13041211. Epub 2012 Jun 28.
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.
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.
These results show that donor forkhead box P3+ T cells infiltrate the deceased donor kidney, where they may control inflammatory and injury responses.
叉头框 P3 调节性 T 细胞可控制炎症反应，但尚不清楚其是否可抑制脑死亡引发的炎症和死亡供体肾脏的组织损伤。
设计、设置、参与者、测量：为了研究调节性 T 细胞在捐赠和移植过程的各个阶段的作用，在死亡和活体供体的肾活检组织 0 时相，测定了叉头框 P3、调节性和炎性细胞因子表达以及组织损伤标志物。此外，还研究了激活的原代肾小管上皮细胞中叉头框 P3+T 细胞与肾脏损伤分子-1 的相互作用。
冷保存后，死亡供体肾脏表达更高的肾脏损伤分子-1 和 CD3εmRNA 水平。与活体供体肾脏相比，这些样本中的炎性细胞因子 IL-8 和 IFN-γ 以及与调节相关的标志物（叉头框 P3、TGF-β 和 IL-10）表达较高。发现叉头框 P3mRNA 表达水平与肾脏损伤分子-1 和叉头框 P3 与 IFN-γ 之间存在相关性。免疫组化分析证实供体肾脏存在叉头框 P3+T 细胞。移植后第一周的肾功能（通过血清肌酐水平分析）与肾脏损伤分子-1 和叉头框 P3mRNA 水平相关。体外研究显示，与对照 T 细胞相比，原代肾小管上皮细胞与调节性 T 细胞共培养时肾脏损伤分子-1 的表达降低 63%（平均值）。
这些结果表明，供体叉头框 P3+T 细胞浸润死亡供体肾脏，在那里它们可能控制炎症和损伤反应。
