Samoilova E B, Horton J L, Zhang H, Chen Y
Institute for Human Gene Therapy, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
J Mol Med (Berl). 1997 Aug;75(8):603-8. doi: 10.1007/s001090050145.
Although it is well established that CD40 and its ligand (CD40L) play pivotal roles in the development of humoral immunity, their roles in cell-mediated immunity and cell-mediated autoimmune diseases are not well defined. We report here that CD40:CD40L interaction is crucial for the development of experimental autoimmune encephalomyelitis (EAE), a prototype TH1-cell mediated autoimmune disease. Specific blockade of CD40L at the time of immunization markedly suppressed the incidence, mortality, day of onset, and clinical scores of EAE in (PLJ x SJL) F1 mice. Importantly, the disease suppression was not associated with anergy or deletion of autoreactive T cells but was accompanied by a drastic alteration of their cytokine profiles. The production of interferon (IFN)-gamma was markedly suppressed while that of interleukin (IL)-4 enhanced. These results suggest that CD40:CD40L interaction plays important roles in the differentiation of autoreactive TH1 versus TH2 cells in vivo, and that CD40L blockade is effective in preventing autoimmune encephalomyelitis.
尽管CD40及其配体（CD40L）在体液免疫的发展中起着关键作用，但它们在细胞介导的免疫和细胞介导的自身免疫性疾病中的作用尚未明确界定。我们在此报告，CD40:CD40L相互作用对于实验性自身免疫性脑脊髓炎（EAE）的发展至关重要，EAE是一种典型的TH1细胞介导的自身免疫性疾病。在免疫时特异性阻断CD40L可显著抑制（PLJ×SJL）F1小鼠EAE的发病率、死亡率、发病天数和临床评分。重要的是，疾病抑制与自身反应性T细胞的无反应性或缺失无关，而是伴随着它们细胞因子谱的剧烈改变。干扰素（IFN）-γ的产生显著受到抑制，而白细胞介素（IL）-4的产生增强。这些结果表明，CD40:CD40L相互作用在体内自身反应性TH1细胞与TH2细胞的分化中起重要作用，并且阻断CD40L在预防自身免疫性脑脊髓炎方面是有效的。
