Binder T A, Greiner D L, Grunnet M, Goldschneider I
Department of Pathology, School of Medicine, University of Connecticut Health Center, Farmington 06030.
J Neuroimmunol. 1993 Jan;42(1):23-32. doi: 10.1016/0165-5728(93)90208-g.
SJL/J mice are highly susceptible to actively induced experimental allergic encephalomyelitis (EAE), whereas B10.S mice are resistant. However, both strains share the H-2s haplotype. We have previously shown that the relative susceptibility of SJL/J and B10.S mice to acute EAE correlates, respectively, with high and low responsiveness to myelin basic protein (MBP), as determined by cloning and limiting dilution analysis of in vitro T cell proliferation. Here, we have investigated the ability of SJL/J and B10.S mice to generate EAE-effector T cells in vivo. We have developed a new mouse strain, B10.S Thy 1.1, that differs at the Thy 1 locus from SJL/J and B10.S mice (both Thy 1.2) but has the same MHC and resistance pattern to EAE as do B10.S mice. Using radiation bone marrow chimeras formed between SJL/J and B10.S Thy 1.1 mice, we have shown that a population of radiosensitive prethymic cells in SJL/J bone marrow has an intrinsic potential to generate EAE-effector T cells, whereas that in B10.S Thy 1.1 bone marrow does not. This lack of detectable EAE effector cells in B10.S Thy 1.1 mice does not appear to be due to the generation of suppressor T cells or to a defect in antigen-presenting cells. Moreover, the potential of SJL/J bone marrow to generate EAE-effector T cells is not inhibited by the concomitant presence of B10.S Thy 1.1 bone marrow cells, thymocytes or dendritic cells in mixed chimeras. Hence, the relative susceptibility of SJL/J and B10.S mice to EAE appears to be directly related to the respective responder status of their T cells to MBP, as evidenced by their ability (or inability) to generate EAE-effector T cells. This high and low responder status appears in turn to be linked to non-MHC background genes, although this has not been established formally.
SJL/J小鼠对主动诱导的实验性自身免疫性脑脊髓炎（EAE）高度易感，而B10.S小鼠则具有抗性。然而，这两个品系都具有H-2s单倍型。我们之前已经表明，通过体外T细胞增殖的克隆和有限稀释分析确定，SJL/J和B10.S小鼠对急性EAE的相对易感性分别与对髓鞘碱性蛋白（MBP）的高反应性和低反应性相关。在这里，我们研究了SJL/J和B10.S小鼠在体内产生EAE效应T细胞的能力。我们培育了一种新的小鼠品系B10.S Thy 1.1，它在Thy 1位点上与SJL/J和B10.S小鼠（均为Thy 1.2）不同，但具有与B10.S小鼠相同的MHC和对EAE的抗性模式。利用SJL/J和B10.S Thy 1.1小鼠之间形成的辐射骨髓嵌合体，我们已经表明，SJL/J骨髓中的一群辐射敏感的胸腺前体细胞具有产生EAE效应T细胞的内在潜力，而B10.S Thy 1.1骨髓中的细胞则没有。B10.S Thy 1.1小鼠中缺乏可检测到的EAE效应细胞似乎不是由于抑制性T细胞的产生或抗原呈递细胞的缺陷。此外，在混合嵌合体中，B10.S Thy 1.1骨髓细胞、胸腺细胞或树突状细胞的同时存在并不抑制SJL/J骨髓产生EAE效应T细胞的潜力。因此，SJL/J和B10.S小鼠对EAE的相对易感性似乎与其T细胞对MBP的各自反应状态直接相关，这通过它们产生（或不产生）EAE效应T细胞的能力得到证明。这种高反应性和低反应性状态反过来似乎与非MHC背景基因有关，尽管这尚未得到正式证实。
