Retinoid treatment of experimental allergic encephalomyelitis. IL-4 production correlates with improved disease course.
Retinoid treatment of experimental allergic encephalomyelitis. IL-4 production correlates with improved disease course.
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DOI：
10.4049/jimmunol.154.1.450
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发表时间：
1995-01
影响因子：
4.4
通讯作者：
M. Racke;D. Burnett;Seong-Hee Pak;Paul S. Albert;B. Cannella;C. S. Raine;D. McFarlin;Dorothy E. Scott
中科院分区：
文献类型：
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作者：
M. Racke;D. Burnett;Seong-Hee Pak;Paul S. Albert;B. Cannella;C. S. Raine;D. McFarlin;Dorothy E. Scott
实验性过敏性脑脊髓炎（EAE）是一种以中枢神经系统炎症和脱髓鞘为特征的自身免疫性疾病。类视黄醇通过结合并激活视黄酸受体（似乎是核转录因子）来调节细胞分化和生长。研究了类维生素A对髓鞘碱性蛋白（MBP）特异性淋巴结细胞（LNC）转移产生的慢性复发性EAE的影响。全反式视黄酸（tRA）在体外抑制 MBP 特异性 LNC 的增殖。然而，这些细胞转移 EAE 的能力因仅轻度抑制 T 细胞增殖的 tRA 浓度而显着降低。在体外 MBP 特异性 LNC 激活过程中，tRA 的存在导致 IL-4 mRNA 显着增加，而 IL-2、TNF-α 和 IFN-gamma 的 mRNA 减少。在培养物上清液中也检测到增加的 IL-4。然而，在体外 MBP 特异性 LNC 激活过程中，IL-4 中和抗体 (11B11) 的存在并不能逆转 tRA 引起的脑炎抑制。即使在疾病发作后给予，体内给予类视黄醇也能改善临床病程。这些发现表明，tRA 存在下的 T 细胞活化导致 Th2 表型 T 细胞的发育，这反过来可能是 MBP 特异性 T 细胞致脑炎性降低的原因。类视黄醇对由 Th1 样 T 细胞主导的免疫反应调节为以 Th2 样细胞的保护性细胞因子为主的免疫反应，可能与人类脱髓鞘疾病（如多发性硬化症）具有潜在相关性。
Experimental allergic encephalomyelitis (EAE) is an autoimmune disease characterized by central nervous system inflammation and demyelination. Retinoids regulate cell differentiation and growth by binding to and activating retinoic acid receptors, which seem to be nuclear transcription factors. The effect of retinoids on chronic relapsing EAE produced by the transfer of myelin basic protein (MBP)-specific lymph node cells (LNC) was studied. All-trans-retinoic acid (tRA) inhibited the proliferation of MBP-specific LNC in vitro. However, the capacity of these cells to transfer EAE was markedly reduced by concentrations of tRA that only mildly inhibited T cell proliferation. The presence of tRA during in vitro MBP-specific LNC activation resulted in a considerable increase in IL-4 mRNA, whereas mRNA for IL-2, TNF-alpha, and IFN-gamma was decreased. Increased IL-4 also was detected in culture supernatants. However, the presence of a neutralizing Ab to IL-4 (11B11) during MBP-specific LNC activation in vitro did not reverse the inhibition of encephalitogenicity caused by tRA. The administration of retinoids in vivo resulted in an improved clinical course, even when given after disease onset. These findings suggest that T cell activation in the presence of tRA results in the development of T cells of the Th2 phenotype, which, in turn, might be responsible for the decrease in the encephalitogenicity of MBP-specific T cells. The modulation by retinoids of an immune response dominated by Th1-like T cells to one in which the protective cytokines of Th2-like cells predominate may have potential relevance for human demyelinating diseases such as multiple sclerosis.