Seki S, Abo T, Ohteki T, Sugiura K, Kumagai K
Department of Microbiology, Tohoku University School of Dentistry, Sendai, Japan.
J Immunol. 1991 Aug 15;147(4):1214-21.
Autoimmune MRL-lpr/lpr (lpr) mice develop severe lymphadenopathy, characterized by the accumulation of alpha beta-T cells with CD4-8- double negative (DN) phenotype, at the onset of disease. We previously demonstrated that the liver is a major site for the proliferation of such DN alpha beta-T cells. Herein, we further demonstrate that a large proportion of alpha beta-T cells in the liver and other organs, except the thymus, of lpr mice have unique properties, such as DN phenotype, relatively dull TCR intensity, a preponderance of V beta 8+ cells, and Pgp-1 expression. Interestingly, alpha beta-T cells in the liver of normal mice were found to consist of T cells with intermediate intensity of TCR (i.e., brighter than thymic dull TCR and lower than thymic bright TCR) as well as with bright intensity of TCR in the immunofluorescence test. These hepatic alpha beta-T cells with intermediate TCR in normal mice were found to have properties similar to those of alpha beta-T cells in lpr mice. These results suggest that abnormal alpha beta-T cells in lpr mice are a counterpart of normal T cells in the liver. An abnormal expansion of such T cells in the liver might be fundamental to the pathogenesis involved in these autoimmune mice.
自身免疫性MRL-lpr/lpr(lpr)小鼠在疾病发作时会出现严重的淋巴结病,其特征是具有CD4-8-双阴性(DN)表型的αβ-T细胞积聚。我们之前证明肝脏是此类DNαβ-T细胞增殖的主要部位。在此,我们进一步证明,lpr小鼠肝脏和除胸腺外的其他器官中,很大一部分αβ-T细胞具有独特的特性,如DN表型、相对暗淡的TCR强度、Vβ8+细胞占优势以及Pgp-1表达。有趣的是,在免疫荧光试验中发现正常小鼠肝脏中的αβ-T细胞由TCR强度中等(即比胸腺暗淡TCR亮且比胸腺明亮TCR暗)的T细胞以及TCR强度明亮的T细胞组成。发现正常小鼠中这些具有中等TCR的肝脏αβ-T细胞具有与lpr小鼠中αβ-T细胞相似的特性。这些结果表明,lpr小鼠中的异常αβ-T细胞是肝脏中正常T细胞的对应物。此类T细胞在肝脏中的异常扩增可能是这些自身免疫小鼠发病机制的基础。