Krieg A M, Gourley M F, Steinberg A D
Cellular Immunology Section, ARB, NIAMS, National Institutes of Health, Bethesda, MD 20892.
J Immunol. 1991 May 1;146(9):3002-5.
Recent studies of thymic gene expression in murine lupus have demonstrated 8.4-kb (full-length size) modified polytropic (Mpmv) endogenous retroviral RNA. In contrast, normal control mouse strains do not produce detectable amounts of such RNA in their thymuses. Prior studies have attributed a defect in experimental tolerance in murine lupus to a bone marrow stem cell rather than to the thymic epithelium; in contrast, infectious retroviral expression has been associated with the thymic epithelium, rather than with the bone marrow stem cell. The present study was designed to determine whether the abnormal Mpmv expression associated with murine lupus mapped to thymic epithelium or to a marrow precursor. Lethally irradiated control and lupus-prone mice were reconstituted with T cell depleted bone marrow; one month later their thymuses were studied for endogenous retroviral RNA and protein expression. Recipients of bone marrow from nonautoimmune donors expressed neither 8.4-kb Mpmv RNA nor surface MCF gp70 in their thymuses. In contrast, recipients of bone marrow from autoimmune NZB or BXSB donors expressed thymic 8.4-kb Mpmv RNA and mink cell focus-forming gp70. These studies demonstrate that lupus-associated 8.4-kb Mpmv endogenous retroviral expression is determined by bone marrow stem cells.
最近对小鼠狼疮中胸腺基因表达的研究已经证实了8.4千碱基对（全长大小）的修饰多嗜性（Mpmv）内源性逆转录病毒RNA。相比之下，正常对照小鼠品系在其胸腺中不会产生可检测量的此类RNA。先前的研究将小鼠狼疮实验性耐受性的缺陷归因于骨髓干细胞而非胸腺上皮；相反，传染性逆转录病毒表达与胸腺上皮相关，而非与骨髓干细胞相关。本研究旨在确定与小鼠狼疮相关的异常Mpmv表达定位于胸腺上皮还是骨髓前体细胞。用T细胞耗竭的骨髓重建经致死性照射的对照小鼠和易患狼疮的小鼠；一个月后，研究它们胸腺中的内源性逆转录病毒RNA和蛋白质表达。来自非自身免疫供体的骨髓受体在其胸腺中既不表达8.4千碱基对的Mpmv RNA，也不表达表面MCF gp70。相比之下，来自自身免疫性NZB或BXSB供体的骨髓受体表达胸腺8.4千碱基对的Mpmv RNA和貂细胞集落形成gp70。这些研究表明，与狼疮相关的8.4千碱基对Mpmv内源性逆转录病毒表达由骨髓干细胞决定。
