Masuda T, Ohteki T, Abo T, Seki S, Nose S, Nagura H, Kumagai K
Second Department of Pathology, Tohoku University School of Medicine, Japan.
J Immunol. 1991 Nov 1;147(9):2907-12.
There have been several reports that double negative (DN) CD4-8- T alpha beta-cells might be responsible for the onset of autoimmune diseases in humans and mice. We previously revealed that such DN T alpha beta-cells are generated in the liver of autoimmune MRL-lpr/lpr mice. In the present study, we further characterize the histology of the liver in these mice by light and electron microscopic studies. An intensive accumulation of mononuclear cells in the liver was demonstrated and a significant proportion of these mononuclear lymphocytes was found to intimately interact with Kupffer cells or endothelial cells of the hepatic sinusoids. The majority of such lymphocytes were TcR+CD4-8-Pgp-1+ alpha beta-cells. Identification of DN T alpha beta-cells was then performed in various autoimmune model mice. Interestingly, all autoimmune mice tested (i.e., MRL-lpr/lpr, C3H/HeJ-gld/gld, BXSB, NOD, MRL(-)+/+ and NZB/W F1 mice), showed an increased proportion of DN T alpha beta-cells (greater than 11% among all MNC) in the liver when they became old and diseased. On the other hand, young and old normal mice and young autoimmune mice before the onset of disease did not have such a high proportion of DN T alpha beta-cells (less than 10%) in the liver. Among autoimmune mice, MRL-lpr/lpr and C3H/HeJ-gld/gld mice had lymphadenopathy, which consisted of DN T alpha beta-cells (greater than 25%), after the onset of disease. Autoimmune mice of the other strains had neither lymphadenopathy nor DN T alpha beta-cells in the periphery, even when they were diseased. These results suggest that the expansion of the DN T alpha beta-cell population in the liver is a common feature of autoimmune mice, irrespective of the information of lymphadenopathy.
有几份报告指出，双阴性（DN）CD4 - 8 - Tαβ细胞可能是人类和小鼠自身免疫性疾病发病的原因。我们之前发现，此类DN Tαβ细胞是在自身免疫性MRL - lpr/lpr小鼠的肝脏中产生的。在本研究中，我们通过光学显微镜和电子显微镜研究进一步对这些小鼠肝脏的组织学特征进行了描述。结果显示肝脏中有大量单核细胞积聚，并且发现这些单核淋巴细胞中有很大一部分与肝窦的库普弗细胞或内皮细胞密切相互作用。这些淋巴细胞中的大多数是TcR + CD4 - 8 - Pgp - 1 +αβ细胞。然后在各种自身免疫模型小鼠中进行了DN Tαβ细胞的鉴定。有趣的是，所有测试的自身免疫小鼠（即MRL - lpr/lpr、C3H/HeJ - gld/gld、BXSB、NOD、MRL（-） +/+和NZB/W F1小鼠）在年老患病时，肝脏中DN Tαβ细胞的比例增加（在所有单核细胞中大于11%）。另一方面，年轻和年老的正常小鼠以及疾病发作前的年轻自身免疫小鼠肝脏中DN Tαβ细胞的比例并不高（小于10%）。在自身免疫小鼠中，MRL - lpr/lpr和C3H/HeJ - gld/gld小鼠在疾病发作后出现了淋巴结病，其中DN Tαβ细胞占比（大于25%）。其他品系的自身免疫小鼠即使患病，外周也没有淋巴结病和DN Tαβ细胞。这些结果表明，肝脏中DN Tαβ细胞群体的扩增是自身免疫小鼠的一个共同特征，与淋巴结病情况无关。
