Studies of lymphoproliferation in MRL-lpr/lpr mice.
Studies of lymphoproliferation in MRL-lpr/lpr mice.
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MRL-lpr/lpr 小鼠淋巴增殖的研究。
DOI：
10.4049/jimmunol.133.4.1955
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发表时间：
1984
影响因子：
4.4
通讯作者：
A. Steinberg
中科院分区：
文献类型：
--
作者：
P. Smathers;T. Santoro;T. Chused;J. P. Reeves;A. Steinberg
MRL-LPR/LPR小鼠出现大规模的淋巴增殖和相关的自身免疫过程，包括抗DNA形成、血管炎和肾小球肾炎。我们对MRL-LPR/LPR小鼠的淋巴增殖进行了研究，发现多种因素是起作用的。虽然新生儿胸腺切除明显延缓了综合征的发生，但长期注射聚rI.rC可以替代胸腺。所获得的细胞具有异常的MRL-LPR/LPR T细胞的表型特征，Thy-1+，Dull Ly-1+，Lyt-2-，6b2+，Ig-。2周龄时的脾切除明显延缓了这种综合征的发展；然而，出生时的脾切除并不能。5周时切除脾可起到一定的保护作用。因此，在MRL-LPR/LPR小鼠的生命中似乎有一个关键时期，当脾对淋巴增殖起重要作用时。最值得注意的是，肾被膜下的MRL-LPR/LPR脾移植可诱导MRL+/+受体LPR/LPR小鼠特有的淋巴结病。移植物内的细胞必须能够增殖才能发生腺病，因为就在移植前用800R照射脾消除了诱发淋巴病变的潜力。在+/+小鼠体内植入+/+脾未引起腺病。虽然MRL-LPR/LPR雄性的发病速度比雌性稍慢，但差异很小。延缓疾病的操作，如2周的脾切除或新生儿胸腺切除，放大了性别差异。雄性MRL-LPR/LPR小鼠在切除胸腺和脾并给予多克隆免疫激活剂后，既没有出现抗DNA抗体，也没有出现淋巴病变，而它们的雌性后代同时表现出这两种异常。我们从这些研究中得出结论，多种因素对MRL-LPR/LPR小鼠的淋巴增殖和自身免疫综合征的大小起调节作用。
MRL-lpr/lpr mice develop massive lymphoproliferation and an associated autoimmune process that includes anti-DNA formation, vasculitis, and glomerulonephritis. We have investigated the lymphoproliferation of MRL-lpr/lpr mice and have found that multiple factors are operative. Although neonatal thymectomy markedly retards the syndrome, chronic injection of poly rI.rC could substitute for the thymus. The resulting cells had the phenotype characteristic of the abnormal MRL-lpr/lpr T cells, Thy-1+, dull Ly-1+, Lyt-2-, 6B2+, Ig-. Splenectomy at 2 wk of age markedly retarded the development of this syndrome; however, splenectomy at birth did not. Some protection was afforded by splenectomy at 5 wk. Thus, there appears to be a critical period in the life of an MRL-lpr/lpr mouse when the spleen contributes importantly to the lymphoproliferation. A most remarkable observation was that an MRL-lpr/lpr spleen graft under the kidney capsule could induce lymphadenopathy characteristic of lpr/lpr mice in MRL +/+ recipients. Cells within the graft had to be able to proliferate for the adenopathy to occur because irradiation of the spleen with 800 R just before grafting abrogated the lymphadenopathy-inducing potential. No adenopathy was induced by +/+ spleen grafts placed into +/+ mice. Although MRL-lpr/lpr males develop disease slightly more slowly than female littermates, the differences are small. Manipulations that retard disease, such as splenectomy at 2 wk or neonatal thymectomy, magnified the sex differences. Male MRL-lpr/lpr mice that were thymectomized and splenectomized and given polyclonal immune activators failed to develop either anti-DNA or lymphadenopathy, whereas their female littermates expressed both abnormalities. We conclude from these studies that multiple factors serve to modulate the magnitude of the lymphoproliferation and autoimmune syndrome of MRL-lpr/lpr mice.