Schoenberger S P, Toes R E, van der Voort E I, Offringa R, Melief C J
Department of Immunohematology and Blood Bank, University Hospital Leiden, The Netherlands.
Nature. 1998 Jun 4;393(6684):480-3. doi: 10.1038/31002.
Although in vivo priming of CD8+ cytotoxic T lymphocytes (CTLs) generally requires the participation of CD4+ T-helper lymphocytes, the nature of the 'help' provided to CTLs is unknown. One widely held view is that help for CTLs is mediated by cytokines produced by T-helper cells activated in proximity to the CTL precursor at the surface of an antigen-presenting cell (APC). An alternative theory is that, rather than being directly supplied to the CTL by the helper cell, help is delivered through activation of the APC, which can then prime the CTL directly. CD40 and its ligand, CD40L, may activate the APC to allow CTL priming. CD40L is expressed on the surface of activated CD4+ T-helper cells and is involved in their activation and in the development of their effector functions. Ligation of CD40 on the surface of APCs such as dendritic cells, macrophages and B cells greatly increases their antigen-presentation and co-stimulatory capacity. Here we report that signalling through CD40 can replace CD4+ T-helper cells in priming of helper-dependent CD8+ CTL responses. Blockade of CD40L inhibits CTL priming; this inhibition is overcome by signalling through CD40. CD40-CD40L interactions are therefore vital in the delivery of T-cell help for CTL priming.
虽然体内CD8+细胞毒性T淋巴细胞（CTL）的致敏通常需要CD4+辅助性T淋巴细胞的参与，但向CTL提供的“辅助”的本质尚不清楚。一种广泛持有的观点是，对CTL的辅助由在抗原呈递细胞（APC）表面靠近CTL前体处被激活的辅助性T细胞产生的细胞因子介导。另一种理论是，辅助并非由辅助性细胞直接提供给CTL，而是通过激活APC来传递，然后APC可直接致敏CTL。CD40及其配体CD40L可能激活APC以允许CTL致敏。CD40L表达于活化的CD4+辅助性T细胞表面，参与其激活及其效应功能的发挥。在诸如树突状细胞、巨噬细胞和B细胞等APC表面的CD40的结合极大地增强了它们的抗原呈递和共刺激能力。我们在此报告，通过CD40发出的信号可在辅助依赖性CD8+CTL反应的致敏中替代CD4+辅助性T细胞。阻断CD40L会抑制CTL致敏；通过CD40发出的信号可克服这种抑制。因此，CD40 - CD40L相互作用在为CTL致敏提供T细胞辅助方面至关重要。
