Biancone L, Andres G, Ahn H, Lim A, Dai C, Noelle R, Yagita H, De Martino C, Stamenkovic I
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02129, USA.
J Exp Med. 1996 Apr 1;183(4):1473-81. doi: 10.1084/jem.183.4.1473.
We assessed the role of CD40-CD40L, cytotoxic T lymphocyte (CTL)A4/CD28-B7s, and CD2-CD48/CD58 lymphocyte costimulatory pathways in the development of mercury chloride (HgCl2)-induced autoimmune disease in mice, which is believed to be mediated by T helper (Th) subset Th2. Inhibition of CD40-CD40-L and CTLA4/CD28-B7s interactions by anti-CD40-L antibody and soluble CTLA4-immunoglobulin (Ig) fusion protein, respectively, abrogated the autoimmune disease without affecting interleukin 4 (IL-4) production, showing the importance of physical contact between T and B lymphocytes in the Th2-mediated process. In contrast, two anti-CD2 antibodies that have been shown to induce immunosuppression of Th1-mediated events exacerbated the autoantibody response and augmented IgG1, IgE, and IL-4 production, transforming a mild mesangial glomerulopathy into a severe systemic immune complex disease. These observations demonstrate that manipulation of lymphocyte accessory counterreceptor interactions may affect the course of Th2-associated autoimmune disease and suggest that signals resulting from CD2 engagement play an essential role in the regulation of the Th1-Th2 effector equilibrium.
我们评估了CD40-CD40L、细胞毒性T淋巴细胞（CTL）A4/CD28-B7以及CD2-CD48/CD58淋巴细胞共刺激途径在氯化汞（HgCl2）诱导的小鼠自身免疫性疾病发展中的作用，该疾病被认为是由辅助性T细胞（Th）亚群Th2介导的。分别用抗CD40-L抗体和可溶性CTLA4-免疫球蛋白（Ig）融合蛋白抑制CD40-CD40-L和CTLA4/CD28-B7的相互作用，可消除自身免疫性疾病，且不影响白细胞介素4（IL-4）的产生，这表明T淋巴细胞和B淋巴细胞之间的物理接触在Th2介导的过程中具有重要性。相比之下，两种已被证明可诱导Th1介导事件免疫抑制的抗CD2抗体加剧了自身抗体反应，并增加了IgG1、IgE和IL-4的产生，将轻度系膜性肾小球病转变为严重的系统性免疫复合物疾病。这些观察结果表明，操纵淋巴细胞辅助性反受体相互作用可能会影响Th2相关自身免疫性疾病的进程，并提示CD2结合产生的信号在Th1-Th2效应器平衡的调节中起重要作用。
