Katagiri T, Cohen P L, Eisenberg R A
Department of Medicine, University of North Carolina, Chapel Hill 27599.
J Exp Med. 1988 Mar 1;167(3):741-51. doi: 10.1084/jem.167.3.741.
The lpr gene induces marked lymphoproliferation characterized by the massive accumulation of T cells of an unusual phenotype and concomitant autoimmune disease. To clarify the mechanism of the lpr effect, bone marrow cells from B6-lpr/lpr (Ly-1.2) and B6-+/+ (Ly-1.1) mice were transferred into lethally irradiated B6-lpr/lpr mice. As has been previously reported, recipients of the B6-lpr/lpr bone marrow showed the typical lpr phenotype with marked lymphadenopathy, splenomegaly and increased levels of autoantibodies; while the recipients of B6-+/+ bone marrow had normal sized lymph nodes and spleen and no autoantibodies. A third group of mice received an equal mixture of bone marrow cells from the B6-lpr/lpr and B6-+/+ donors. These mice showed both lymphadenopathy and autoantibody production comparable to that of recipients of the B6-lpr/lpr marrow alone. Immunofluorocytometric analysis of the lymphoid populations in these mixed bone marrow recipients established that the T cells from the lpr/lpr and +/+ donors were equivalently represented in the peripheral blood and thymus. In striking contrast, the T cells that accumulated in abnormally large numbers in the lymph nodes were almost entirely from the lpr donor. Their surface phenotype was Thy-1+(dull), Ly-1.2+(dull), Lyt-2-, L3T4-, 9F3+, and 3A1+, which is consistent with that found in intact lpr mice. These results indicate that the lpr gene causes an intrinsic defect directly within the T cells that accumulate in large numbers in lpr mice. In addition, the presence of the +/+ T cells cannot prevent the expression of the lpr abnormalities.
lpr基因可诱导显著的淋巴细胞增殖，其特征为大量异常表型的T细胞积聚以及伴随的自身免疫性疾病。为阐明lpr效应的机制，将B6-lpr/lpr（Ly-1.2）和B6-+/+（Ly-1.1）小鼠的骨髓细胞移植到经致死剂量照射的B6-lpr/lpr小鼠体内。如先前报道，接受B6-lpr/lpr骨髓的受体表现出典型的lpr表型，伴有明显的淋巴结病、脾肿大和自身抗体水平升高；而接受B6-+/+骨髓的受体淋巴结和脾脏大小正常，且无自身抗体。第三组小鼠接受来自B6-lpr/lpr和B6-+/+供体的等量混合骨髓细胞。这些小鼠表现出的淋巴结病和自身抗体产生情况与仅接受B6-lpr/lpr骨髓的受体相当。对这些混合骨髓受体的淋巴细胞群体进行免疫荧光细胞分析表明，来自lpr/lpr和+/+供体的T细胞在外周血和胸腺中的比例相当。与之形成显著对比的是，在淋巴结中大量积聚的T细胞几乎全部来自lpr供体。它们的表面表型为Thy-1+(暗淡)、Ly-1.2+(暗淡)、Lyt-2-、L3T4-、9F3+和3A1+，这与在完整的lpr小鼠中发现的表型一致。这些结果表明，lpr基因直接导致了在lpr小鼠中大量积聚的T细胞存在内在缺陷。此外，+/+ T细胞的存在并不能阻止lpr异常表型的表达。
