Perrin P J, Maldonado J H, Davis T A, June C H, Racke M K
Immune Cell Biology Program, Naval Medical Research Institute, Bethesda, MD 20889-5607, USA.
J Immunol. 1996 Aug 15;157(4):1333-6.
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.
抗原呈递细胞（APC）上表达的B7家族细胞表面分子通过CD28或细胞毒性T淋巴细胞相关抗原4（CTLA-4）向T细胞提供辅助信号。然而，虽然CD28转导最佳免疫反应所需的共刺激信号，但CTLA-4传递负信号。这些研究使用抗CTLA-4单克隆抗体（mAb）直接研究这种T细胞表面分子在实验性自身免疫性脑脊髓炎（EAE）中的作用。在初始免疫细胞相互作用期间以及致脑炎性免疫反应的效应阶段评估CTLA-4对疾病的调节作用。抗CTLA-4治疗的效果取决于给药方案。临床症状出现时阻断CTLA-4会显著加重疾病，提高死亡率。疾病加重与致脑炎性细胞因子肿瘤坏死因子-α（TNF-α）、干扰素-γ（IFN-γ）和白细胞介素-2（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，减弱炎性细胞因子的产生和临床疾病表现。
