CTLA-4 blockade enhances clinical disease and cytokine production during experimental allergic encephalomyelitis.
CTLA-4 blockade enhances clinical disease and cytokine production during experimental allergic encephalomyelitis.
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DOI：
10.4049/jimmunol.157.4.1333
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发表时间：
1996-08
影响因子：
4.4
通讯作者：
P. Perrin;J. H. Maldonado;Thomas A. Davis;Carl H. June;M. Racke
中科院分区：
文献类型：
--
作者：
P. Perrin;J. H. Maldonado;Thomas A. Davis;Carl H. June;M. Racke
APC 上表达的 B7 细胞表面分子家族通过 CD28 或 CTLA-4 向 T 细胞提供辅助信号。然而，CD28 转导最佳免疫反应所需的共刺激信号，而 CTLA-4 则传递负信号。这些研究使用抗 CTLA-4 mAb 来直接研究这种 T 细胞表面分子在实验性过敏性脑脊髓炎 (EAE) 中的作用。在初始免疫细胞相互作用和致脑炎免疫反应的效应阶段评估 CTLA-4 对疾病的调节。抗 CTLA-4 治疗的效果取决于时间表。 CTLA-4阻断在临床症状出现期间明显加剧疾病，增加死亡率。疾病恶化与脑炎细胞因子 TNF-α、IFN-γ 和 IL-2 的产生增加有关。因此，CTLA-4 调节 EAE 中自身免疫反应的强度，减弱炎症细胞因子的产生和临床疾病表现。
The B7 family of cell surface molecules expressed on APC provides accessory signals to T cells via either CD28 or CTLA-4. However, while CD28 transduces a costimulatory signal that is required for an optimal immune response, CTLA-4 transmits a negative signal. These studies use an anti-CTLA-4 mAb to directly address the role of this T cell surface molecule in experimental allergic encephalomyelitis (EAE). CTLA-4 regulation of disease was assessed during initial immune cell interactions and during the effector stage of the encephalitogenic immune response. The effects of anti-CTLA-4 treatment were schedule dependent. CTLA-4 blockade during the onset of clinical symptoms markedly exacerbated disease, enhancing mortality. Disease exacerbation was associated with enhanced production of the encephalitogenic cytokines TNF-alpha, IFN-gamma and IL-2. Hence, CTLA-4 regulates the intensity of the autoimmune response in EAE, attenuating inflammatory cytokine production and clinical disease manifestations.