Prevention and treatment of experimental autoimmune encephalomyelitis by soluble CD83.
Prevention and treatment of experimental autoimmune encephalomyelitis by soluble CD83.
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可溶性CD83预防和治疗实验性自身免疫性脑脊髓炎。
DOI：
10.1084/jem.20030973
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发表时间：
2004-08-02
影响因子：
15.3
通讯作者：
Steinkasserer, A
中科院分区：
文献类型：
--
作者：
Zinser, E;Lechmann, M;Golka, A;Lutz, MB;Steinkasserer, A
CD83在树突状细胞（DCs）成熟过程中表达上调，已被广泛用作成熟DCs的标志物。最近，我们报道了人CD83胞外免疫球蛋白结构域（hCD83ext）的重组表达。使用这种可溶性形式的CD83，同种异体以及特异性细胞毒性T淋巴细胞增殖可以在体外被阻断。在这里，我们报告的功能分析可溶性CD83在体内，使用小鼠实验性自身免疫性脑脊髓炎（EAE）作为模型。引人注目的是，只有三次注射可溶性CD83几乎完全阻止了与EAE相关的瘫痪。此外，即使在第二次诱导EAE时，CD83处理的小鼠也受到保护，表明持久的抑制作用。此外，可溶性CD83在不同的治疗环境中强烈减少麻痹。最重要的是，即使治疗延迟到疾病症状完全建立，可溶性CD83也明显减少了瘫痪。此外，当第二次诱导EAE时，可溶性CD83处理的动物也显示出减轻的疾病症状。最后，hCD83ext治疗几乎完全减少了脑和脊髓中的白细胞浸润。总之，这项工作强烈支持可溶性CD83的免疫抑制作用，从而表明其在体内调节免疫疾病中的治疗潜力。
CD83 is up-regulated on the surface of dendritic cells (DCs) during maturation and has been widely used as a marker for mature DCs. Recently, we reported the recombinant expression of the extracellular immunoglobulin domain of human CD83 (hCD83ext). Using this soluble form of CD83, allogeneic as well as specific cytotoxic T lymphocyte proliferation could be blocked in vitro. Here we report the functional analysis of soluble CD83 in vivo, using murine experimental autoimmune encephalomyelitis (EAE) as a model. Strikingly, only three injections of soluble CD83 prevented the paralysis associated with EAE almost completely. In addition, even when the EAE was induced a second time, CD83-treated mice were protected, indicating a long-lasting suppressive effect. Furthermore, soluble CD83 strongly reduced the paralysis in different therapeutic settings. Most important, even when the treatment was delayed until the disease symptoms were fully established, soluble CD83 clearly reduced the paralyses. In addition, also when EAE was induced a second time, soluble CD83-treated animals showed reduced disease symptoms. Finally, hCD83ext treatment almost completely reduced leukocyte infiltration in the brain and in the spinal cord. In summary, this work strongly supports an immunosuppressive role of soluble CD83, thereby indicating its therapeutic potential in the regulation of immune disorders in vivo.
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影响因子：
20.3
作者：
KOZLOW, EJ;WILSON, GL;KEHRL, JH
通讯作者：
KEHRL, JH
影响因子：
4.4
作者：
Scholler, N;Hayden-Ledbetter, M;Ledbetter, JA
通讯作者：
Ledbetter, JA
影响因子：
2.2
作者：
Lutz, MB;Kukutsch, N;Schuler, G
通讯作者：
Schuler, G
影响因子：
1.6
作者：
Lechmann, M;Kremmer, E;Steinkasserer, A
通讯作者：
Steinkasserer, A
影响因子：
5.4
作者：
Kruse, M;Rosorius, O;Steinkasserer, A
通讯作者：
Steinkasserer, A