Fossati L, Takahashi S, Merino R, Iwamoto M, Aubry J P, Nose M, Spach C, Motta R, Izui S
Department of Pathology, University of Geneva, Switzerland.
Int Immunol. 1993 May;5(5):525-32. doi: 10.1093/intimm/5.5.525.
The autosomal recessive mutant gene, lpr, has been shown to accelerate the progression of lupus-like autoimmune disease, which is associated with a massive expansion of a unique CD4-CD8- double-negative T cell subset, in MRL/MpJ mice. Here we report a substrain of MRL/MpJ-lpr/lpr (MRL-lpr) mice which live almost twice as long with delayed development of glomerulonephritis, compared with conventional MRL-lpr mice. This substrain, termed MRL-lpr.II (II for long-lived), develops generalized lymphadenopathy characteristically seen in MRL-lpr mice. However, the expansion of a double negative lpr T cell subset is markedly limited with a mean value of 15% in their lymph nodes compared to about 70% in conventional MRL-lpr mice. Overall production of autoantibodies, such as anti-DNA and rheumatoid factors, does not significantly differ between the two MRL-lpr mice. However, serum levels of cryoglobulins, whose major component is IgG3, are markedly diminished in MRL-lpr.II mice with a parallel decrease in IgG3. Since MRL-lpr.II mice still carry the lpr mutation, as documented by the presence of defects in the Fas antigen, a possible new mutation in this substrain may play a significant role in the pathogenesis of lupus-like autoimmune syndrome.
常染色体隐性突变基因lpr已被证明可加速狼疮样自身免疫性疾病的进展，该疾病与MRL/MpJ小鼠中一种独特的CD4-CD8-双阴性T细胞亚群的大量扩增有关。在此，我们报告了一种MRL/MpJ-lpr/lpr（MRL-lpr）小鼠的亚系，与传统的MRL-lpr小鼠相比，其寿命几乎延长了一倍，肾小球肾炎的发展也有所延迟。这个亚系被称为MRL-lpr.II（II代表长寿），具有MRL-lpr小鼠特有的全身性淋巴结病。然而，双阴性lpr T细胞亚群的扩增明显受限，其淋巴结中的平均值为15%，而传统MRL-lpr小鼠约为70%。两种MRL-lpr小鼠自身抗体（如抗DNA和类风湿因子）的总体产生没有显著差异。然而，MRL-lpr.II小鼠中冷球蛋白的血清水平显著降低，其主要成分是IgG3，同时IgG3也平行下降。由于MRL-lpr.II小鼠仍然携带lpr突变，Fas抗原缺陷的存在证明了这一点，该亚系中可能的新突变可能在狼疮样自身免疫综合征的发病机制中起重要作用。
