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成熟中枢神经系统中的实验性自身免疫性脑脊髓炎。将髓鞘碱性蛋白特异性T系淋巴细胞转移至新生Lewis大鼠。

Experimental autoimmune encephalomyelitis in the maturing central nervous system. Transfer of myelin basic protein-specific T line lymphocytes to neonatal Lewis rats.

作者信息

Umehara F, Qin Y F, Goto M, Wekerle H, Meyermann R

机构信息

Max-Planck-Gesellschaft, Clinical Research Unit for Multiple Sclerosis, Würzburg, Federal Republic of Germany.

出版信息

Lab Invest. 1990 Feb;62(2):147-55.

PMID:1689408
Abstract

We analyzed the effects of myelin basic protein (MBP)-specific encephalitogenic T line cells in neonatal syngeneic recipients before and after formation of central nervous system myelin. Lewis rat pups (postnatal days 0, 1, 2, 4, 8) were injected intraperitoneally with MBP-specific T cell line in doses which cause clinical and histologic changes of experimental autoimmune encephalomyelitis (EAE) in adult rats. We correlated the susceptibility to transferred EAE with the developmental appearance of MBP as demonstrated by immunohistochemical staining. MBP was barely demonstrable until postnatal day 2 but became definitely apparent on postnatal day 4. All newborn rats that were injected on postnatal day 0, 1, 2 failed to develop any apparent clinical signs, but histologically some recipients displayed slight inflammatory cell infiltration of the meninges and subpial lesions limited to the lower spinal cord. In striking contrast, rats that were injected on postnatal day 4 or 8, developed clinical signs and, in particular, many of the older recipients became moribund. Histologically, these animals displayed marked inflammatory cell infiltrations and white matter destruction within the spinal cord. Clinical and histologic severity clearly increased with the recipient's age. Histologically, there were some differences between adult rat EAE and newborn rat EAE. In contrast to adult rat EAE which displayed grey and white matter involvement with marked perivascular mononuclear cell infiltrations, newborn rat EAE typically showed very severe changes with edema formation selectively in the white matter and the cellular infiltrates were dominated by polymorphonuclear cells and macrophages. Newborn T line-mediated EAE thus strikingly resembles hyperacute EAE induced in immunocompromised (irradiated) recipients.

摘要

我们分析了髓鞘碱性蛋白(MBP)特异性致脑炎性T系细胞在新生同基因受体中,于中枢神经系统髓鞘形成前后的作用。将Lewis大鼠幼崽(出生后第0、1、2、4、8天)腹腔注射MBP特异性T细胞系,其剂量可在成年大鼠中引发实验性自身免疫性脑脊髓炎(EAE)的临床和组织学变化。我们将对转移EAE的易感性与免疫组化染色所显示的MBP发育出现情况相关联。直到出生后第2天,MBP几乎无法检测到,但在出生后第4天变得明显可见。所有在出生后第0、1、2天注射的新生大鼠均未出现任何明显的临床症状,但在组织学上,一些受体显示出脑膜有轻微的炎性细胞浸润,且软脑膜下病变仅限于脊髓下部。与之形成鲜明对比的是,在出生后第4天或第8天注射的大鼠出现了临床症状,尤其是许多较大的受体变得濒死。在组织学上,这些动物在脊髓内显示出明显的炎性细胞浸润和白质破坏。临床和组织学严重程度明显随受体年龄增加。在组织学上,成年大鼠EAE和新生大鼠EAE之间存在一些差异。与成年大鼠EAE表现为灰质和白质均受累且伴有明显的血管周围单核细胞浸润不同,新生大鼠EAE通常显示出非常严重的变化,在白质中选择性地形成水肿,且细胞浸润以多形核细胞和巨噬细胞为主。因此,新生T系介导的EAE与免疫受损(经辐射)受体中诱导的超急性EAE极为相似。

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