Ascon Dolores B, Ascon Miguel, Satpute Shailesh, Lopez-Briones Sergio, Racusen Lorraine, Colvin Robert B, Soloski Mark J, Rabb Hamid
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
J Leukoc Biol. 2008 Dec;84(6):1400-9. doi: 10.1189/jlb.0907651. Epub 2008 Sep 2.
Healthy liver, intestine, lung, and skin harbor resident lymphocytes with conventional and unconventional phenotypes. Lymphocytes also have been detected in healthy mice kidneys; however, these cells have not been well studied and have been largely overlooked. To better characterize the intra-renal lymphocytes, we extensively perfused C57BL/6J mice with PBS and then isolated mononuclear cells for flow cytometry analysis. We observed T cells, B cells, and NK cells in normal mice kidneys after extensive perfusion. Approximately 50% of kidney T lymphocytes expressed intermediate levels of CD3 (CD3int T cells). Similar to liver and lung, a high percentage of unconventional CD3+CD4(-)CD8(-) double-negative T cells was observed in normal mice kidneys, from which 11% expressed B220 antigen. Unlike the spleen and blood, the classic CD4+ and CD8+ T lymphocytes in the kidney had a high proportion of activated CD69+ and effector/memory CD44- CD62L ligand phenotypes. Also, a small percentage of CD4+CD25+forkhead box p3+ and NKT cells was observed in perfused and exanguinated kidneys. In addition, a distinct TCR repertoire was found on intra-renal conventional and unconventional T cells compared with those from the spleen. Finally, after 24 h of renal ischemia reperfusion injury (IRI), increased production of cytokines IFN-gamma and TNF-alpha by CD4+ and CD8+ T cells, isolated from perfused kidneys, was observed. These data suggest that some of these cells harbored in the kidney could be implicated in the immune response of the IRI pathogenic process.
健康的肝脏、肠道、肺和皮肤中存在具有传统和非传统表型的驻留淋巴细胞。在健康小鼠的肾脏中也检测到了淋巴细胞;然而,这些细胞尚未得到充分研究,在很大程度上被忽视了。为了更好地表征肾内淋巴细胞,我们用磷酸盐缓冲盐水(PBS)对C57BL/6J小鼠进行了广泛灌注,然后分离单核细胞进行流式细胞术分析。在广泛灌注后,我们在正常小鼠肾脏中观察到了T细胞、B细胞和自然杀伤(NK)细胞。约50%的肾T淋巴细胞表达中等水平的CD3(CD3int T细胞)。与肝脏和肺相似,在正常小鼠肾脏中观察到高比例的非传统CD3+CD4(-)CD8(-)双阴性T细胞,其中11%表达B220抗原。与脾脏和血液不同,肾脏中的经典CD4+和CD8+ T淋巴细胞具有高比例的活化CD69+以及效应/记忆CD44-CD62L配体表型。此外,在灌注和放血后的肾脏中还观察到一小部分CD4+CD25+叉头框p3+和自然杀伤T(NKT)细胞。此外,与来自脾脏的细胞相比,在肾内传统和非传统T细胞上发现了独特的T细胞受体(TCR)库。最后,在肾缺血再灌注损伤(IRI)24小时后,观察到从灌注肾脏中分离的CD4+和CD8+ T细胞产生的细胞因子γ干扰素(IFN-γ)和肿瘤坏死因子-α(TNF-α)增加。这些数据表明,肾脏中存在的这些细胞中的一些可能参与了IRI致病过程的免疫反应。