Expression of costimulatory molecules B7-1 (CD80), B7-2 (CD86), and interleukin 12 cytokine in multiple sclerosis lesions.
Expression of costimulatory molecules B7-1 (CD80), B7-2 (CD86), and interleukin 12 cytokine in multiple sclerosis lesions.
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多发性硬化病变中共刺激分子B7-1（CD80），B7-2（CD86）和白介素12细胞因子的表达。
DOI：
10.1084/jem.182.6.1985
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发表时间：
1995-12-01
影响因子：
15.3
通讯作者：
Hafler, David A.
中科院分区：
文献类型：
--
作者：
Windhagen, Anja;Newcombe, Jia;Dangond, Fernando;Strand, Catherine;Woodroofe, M. Nicola;Cuzner, M. Louise;Hafler, David A.
正常个体的循环中存在静息的自身反应性T细胞，但无病理后果。在自身免疫动物模型中，在共刺激分子B7 - 1存在的情况下刺激这些自身反应性T细胞会导致T细胞介导的自身免疫疾病，而B7 - 2刺激则产生调节性自身反应性T细胞，减轻疾病严重程度。因此，在中枢神经系统（CNS）髓鞘的一种假定自身免疫疾病——多发性硬化症（MS）的病理生理学中，带有共刺激分子的抗原在脑内重新激活髓鞘自身反应性T细胞可能是一个关键事件。我们使用半定量逆转录酶 - 聚合酶链反应和免疫细胞化学方法，对来自15例MS患者和10例对照病例的41个经组织学鉴定的CNS标本进行了细胞因子和共刺激分子的表达研究。在4例病例中，将伴有炎症的血管性CNS梗死与同一大脑的MS斑块进行了比较。我们观察到在急性MS斑块中，尤其是早期病例的斑块中，B7 - 1和白细胞介素（IL）12p40的表达增加，但在炎症性梗死中没有增加。B7 - 1染色主要定位于血管周围炎症套中的淋巴细胞，而非实质细胞。相比之下，B7 - 2主要在不同病程的MS病变以及炎症性梗死中的巨噬细胞上表达。这些发现表明，MS发病的早期事件涉及B7 - 1和IL - 12的上调，从而形成最大程度刺激T细胞活化并诱导T辅助1型免疫反应的条件。
Resting autoreactive T cells are present in the circulation of normal individuals without pathologic consequences. In autoimmune animal models, stimulation of these self-reactive T cells in the presence of costimulatory molecules B7-1 results in T cell-mediated autoimmune disease, whereas B7-2 stimulation generates regulatory autoreactive T cells that abrogate disease severity. Thus, reactivation in the brain of myelin-autoreactive T cells by antigen with costimulatory molecules may be a critical event in the pathophysiology of multiple sclerosis (MS), a putative autoimmune disease of central nervous system (CNS) myelin. We investigated the expression of cytokines and costimulatory molecules in a panel of 41 histologically characterized CNS specimens from 15 MS and 10 control cases using semiquantitative reverse transcriptase-polymerase chain reaction and immunocytochemistry. In four cases, vascular CNS infarcts with inflammation were compared with MS plaques from the same brain. We observed increased expression of B7- 1 and interleukin (IL) 12p40 in acute MS plaques, particularly from early disease cases but not in inflammatory infarcts. B7-1 staining was localized predominantly to the lymphocytes in perivenular inflammatory cuffs but not the parenchyma. In contrast, B7-2 was expressed predominantly on macrophages both in MS lesions of varied time duration and in inflammatory infarcts. These findings indicate that an early event in the initiation of MS involves upregulation of B7-1 and IL-12, resulting in conditions that maximally stimulate T cell activation and induction of T helper 1-type immune responses.
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影响因子：
64.5
作者：
KUCHROO, VK;DAS, MP;GLIMCHER, LH
通讯作者：
GLIMCHER, LH
影响因子：
56.9
作者：
LINSLEY, PS;WALLACE, PM;TEPPER, MA
通讯作者：
TEPPER, MA
影响因子：
56.9
作者：
FREEMAN, GJ;GRIBBEN, JG;NADLER, LM
通讯作者：
NADLER, LM
DOI：
10.1084/jem.170.2.607
发表时间：
1989-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hofman FM;Hinton DR;Johnson K;Merrill JE
通讯作者：
Merrill JE
影响因子：
32.4
作者：
GREEN, JM;NOEL, PJ;THOMPSON, CB
通讯作者：
THOMPSON, CB