Montecino-Rodriguez E M, Loor F
Sandoz Pharma AG, Preclinical Research Basel, Switzerland.
Immunology. 1991 Sep;74(1):127-31.
The generalized lymphoproliferative disease (gld) and lymphoproliferation (lpr) mutations induce the development of strikingly similar autoimmune and lymphoproliferative syndromes in C57BL/6 mice (B6). These syndromes are characterized by hyperglobulinaemia, high levels of circulating autoantibodies and significant splenomegaly and lymphadenopathy resulting principally from the accumulation of a double negative CD4/CD8 T-cell population. These similarities led to the suggestion that the gld and lpr mutations affect two different steps of a common metabolic pathway controlling the differentiation of the T cells. By transferring haematopoietic cells into sublethally irradiated recipients we provide evidence for the different aetiology of the gld- and lpr-induced syndromes. The [gld----gld] chimaeras developed a gld-induced syndrome, like the [lpr----lpr] chimaeras developed a lpr-induced syndrome. However, in contrast to the severe lymphoid aplasia observed in the [lpr----wild] chimaeras, the [gld----wild] chimaeras showed an attenuated form of the gld-induced syndrome. The [lpr----gld] chimaeras developed a lymphoid aplasia (as in the [lpr----wild] chimaeras). This result shows that the gld environment cannot substitute for the lpr environment and allow for the emergence of an lpr-induced pathology.
全身性淋巴细胞增生性疾病（gld）和淋巴细胞增生（lpr）突变在C57BL/6小鼠（B6）中诱发了极为相似的自身免疫和淋巴细胞增生综合征。这些综合征的特征包括高球蛋白血症、循环自身抗体水平升高以及显著的脾肿大和淋巴结病，主要是由于双阴性CD4/CD8 T细胞群体的积累所致。这些相似之处表明，gld和lpr突变影响了控制T细胞分化的共同代谢途径的两个不同步骤。通过将造血细胞移植到亚致死剂量照射的受体中，我们为gld和lpr诱导综合征的不同病因提供了证据。[gld----gld]嵌合体出现了gld诱导的综合征，就像[lpr----lpr]嵌合体出现了lpr诱导的综合征一样。然而，与在[lpr----野生型]嵌合体中观察到的严重淋巴细胞发育不全相反，[gld----野生型]嵌合体表现出gld诱导综合征的一种减轻形式。[lpr----gld]嵌合体出现了淋巴细胞发育不全（如同在[lpr----野生型]嵌合体中那样）。这一结果表明，gld环境不能替代lpr环境并允许lpr诱导的病理状态出现。
