Scholer Alix, Hugues Stéphanie, Boissonnas Alexandre, Fetler Luc, Amigorena Sebastian
Centre de Recherche, Institut Curie, Paris, France.
Immunity. 2008 Feb;28(2):258-70. doi: 10.1016/j.immuni.2007.12.016.
The initiation of cytotoxic immune responses requires the direct interaction between naive CD8+ T lymphocytes and dendritic cells (DCs). Multiphoton imaging in intact lymph nodes (LNs) showed that during priming, naive T cells and DCs establish sequentially brief (i.e., minutes) and long (hours) antigen-specific contacts. We show here that the expression of the Intercellular Adhesion Molecule-1 (ICAM-1) by mature DCs is critical for long-lasting contacts with CD8+ T cells but dispensable for short-lived antigen-specific interactions. Serial brief DC-T cell contacts induced early CD8+ T cell activation, proliferation, and differentiation into effector cytotoxic T lymphocytes in the first few days after immunization. ICAM-1-deficient mature DCs, however, failed to induce fully effective priming, because CD8+ T cells produced reduced amounts of interferon gamma and were clonally depleted after 2 weeks. In addition, Icam1(-/-) mice failed to respond to rechallenge. We conclude that ICAM-1-dependent long-lasting interactions between mature DCs and naive CD8+ T cells determine the survival of activated CD8+ T cells and the establishment of effective memory.
细胞毒性免疫反应的启动需要初始CD8 + T淋巴细胞与树突状细胞（DC）之间的直接相互作用。对完整淋巴结（LN）进行的多光子成像显示，在致敏过程中，初始T细胞和DC会依次建立短暂（即数分钟）和长期（数小时）的抗原特异性接触。我们在此表明，成熟DC表达的细胞间黏附分子1（ICAM-1）对于与CD8 + T细胞的持久接触至关重要，但对于短暂的抗原特异性相互作用则并非必需。在免疫后的头几天，连续的短暂DC-T细胞接触可诱导早期CD8 + T细胞活化、增殖并分化为效应细胞毒性T淋巴细胞。然而，缺乏ICAM-1的成熟DC无法诱导完全有效的致敏，因为CD8 + T细胞产生的干扰素γ量减少，并且在2周后发生克隆性耗竭。此外，Icam1（-/-）小鼠对再次攻击无反应。我们得出结论，成熟DC与初始CD8 + T细胞之间依赖ICAM-1的持久相互作用决定了活化CD8 + T细胞的存活以及有效记忆的建立。
