Ascon Dolores B, Lopez-Briones Sergio, Liu Manchang, Ascon Miguel, Savransky Vladimir, Colvin Robert B, Soloski Mark J, Rabb Hamid
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
J Immunol. 2006 Sep 1;177(5):3380-7. doi: 10.4049/jimmunol.177.5.3380.
T and B lymphocytes have been implicated in the pathogenesis of renal ischemia reperfusion injury (IRI). The trafficking of lymphocytes into kidneys during IRI has been postulated to underlie this effect, but has not been rigorously studied. We therefore characterized the lymphocyte populations infiltrating into mouse kidneys 3 and 24 h after renal IRI. Immunohistochemistry and flow cytometry staining of kidney lymphocytes showed increased trafficking of CD3+ T cells and CD19+ B cells in both sham-operated and IRI mice 3 h after renal IRI. In the IRI mice, increased infiltration of NK1.1+ and CD4+ NK1.1+ cells compared with normal and sham-operated mice was observed 3 and 24 h after renal IRI, respectively. After 24 h of renal IRI, the decreased percentages of CD3+, CD19+, and NK1.1+ populations in the IRI mice compared with control groups were observed. Increased TNF-alpha and IFN-gamma production of kidney infiltration CD3+ T cells in IRI mice but not sham-operated mice was found. Unexpectedly, isolation and transfer of kidney-infiltrating lymphocytes 24 h after renal IRI into T cell-deficient mice reduced their functional and histological injury after renal IRI, suggesting that kidney-infiltrating lymphocytes could have a protective function. These quantitative, qualitative, and functional changes in kidney lymphocytes provide mechanistic insight into how lymphocytes modulate IRI, as well as demonstrating that abdominal surgery alone leads to lymphocyte changes in kidney.
T淋巴细胞和B淋巴细胞与肾缺血再灌注损伤（IRI）的发病机制有关。IRI期间淋巴细胞向肾脏的迁移被认为是造成这种影响的原因，但尚未得到严格研究。因此，我们对肾IRI后3小时和24小时浸润到小鼠肾脏中的淋巴细胞群体进行了特征分析。对肾脏淋巴细胞进行免疫组织化学和流式细胞术染色显示，在肾IRI后3小时，假手术组和IRI小鼠中CD3⁺ T细胞和CD19⁺ B细胞的迁移均增加。在IRI小鼠中，分别在肾IRI后3小时和24小时观察到，与正常小鼠和假手术组小鼠相比，NK1.1⁺和CD4⁺ NK1.1⁺细胞的浸润增加。肾IRI 24小时后，观察到IRI小鼠中CD3⁺、CD19⁺和NK1.1⁺细胞群的百分比与对照组相比有所下降。发现IRI小鼠而非假手术组小鼠中，肾脏浸润的CD3⁺ T细胞产生的肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）增加。出乎意料的是，肾IRI 24小时后，将肾脏浸润淋巴细胞分离并转移到T细胞缺陷小鼠中，可减轻它们在肾IRI后的功能和组织学损伤，这表明肾脏浸润淋巴细胞可能具有保护作用。肾脏淋巴细胞的这些定量、定性和功能变化为淋巴细胞如何调节IRI提供了机制性见解，同时也证明了单纯腹部手术会导致肾脏淋巴细胞发生变化。
