Nagel T, Kalden J R, Manger B
Medizinische Klinik III und Institut für Klinische Immunologie, Friedrich-Alexander-Universität Erlangen-Nürnberg.
Med Klin (Munich). 1998 Oct 15;93(10):592-7. doi: 10.1007/BF03042674.
T CELL RESPONSE: T lymphocytes play a key role in the coordination of the immune response. T helper cells contribute primarily by means of cytokine release, whereas cytotoxic T cells eliminate cells bearing antigens recognized as foreign. Through its T cell receptor each T cell can recognize a specific peptide antigen, which is presented in the context of the major histocompatibility complex (MHC) to T helper cells by specialized antigen-presenting cells or to cytotoxic T cells by nearly all body cells. Upon contact with its specific antigen, the T cell receptor transduces an activation signal into the T cell, leading to proliferation, cytokine production, or efficient cytotoxicity.
However, a second costimulatory signal is necessary to achieve complete activation. This can be provided by the accessory T cell molecule CD28 upon binding to its respective ligands B7-1 (CD80) or B7-2 (CD86). The same ligands bind to CTLA-4 (CD152), a receptor expressed at the surface of T cells previously activated for 2 to 3 days and capable of downregulating activation. IMMUNOSUPPRESSION BY CTLA-4Ig: A genetically engineered soluble fusion protein containing the extracellular domain of CTLA-4 and the Fc portion of an immunoglobulin heavy chain (CTLA-4Ig) prevents the interaction of CD28 and CTLA-4 with their B7 ligands, the subsequent activation of T cells and thereby eliminates or reduces unfavorable immune system activation in transplant rejection or autoimmunity.
The importance of the regulatory system comprising CD28, CTLA-4 and the B7 molecules and its modulation by CTLA-4Ig has been demonstrated in a substantial number of animal models in recent years and holds promise as a novel approach for therapeutic immunomodulation in humans.
T细胞反应：T淋巴细胞在免疫反应的协调中起关键作用。辅助性T细胞主要通过细胞因子释放发挥作用，而细胞毒性T细胞则清除携带被识别为外来抗原的细胞。每个T细胞通过其T细胞受体能够识别特定的肽抗原，该抗原由专门的抗原呈递细胞在主要组织相容性复合体（MHC）的背景下呈递给辅助性T细胞，或由几乎所有体细胞呈递给细胞毒性T细胞。T细胞与其特定抗原接触后，T细胞受体将激活信号转导至T细胞，导致增殖、细胞因子产生或有效的细胞毒性。
然而，要实现完全激活，还需要第二个共刺激信号。这可以由辅助性T细胞分子CD28与其各自的配体B7-1（CD80）或B7-2（CD86）结合来提供。相同的配体与CTLA-4（CD152）结合，CTLA-4是一种在先前激活2至3天的T细胞表面表达的受体，能够下调激活。CTLA-4Ig的免疫抑制作用：一种基因工程可溶性融合蛋白，包含CTLA-4的细胞外结构域和免疫球蛋白重链的Fc部分（CTLA-4Ig），可阻止CD28和CTLA-4与其B7配体的相互作用，从而防止T细胞随后的激活，进而消除或减少移植排斥或自身免疫中不利的免疫系统激活。
近年来，在大量动物模型中已证明了由CD28、CTLA-4和B7分子组成的调节系统的重要性及其通过CTLA-4Ig的调节作用，有望成为人类治疗性免疫调节的新方法。
