Liechtenstein Therese, Dufait Ines, Lanna Alessio, Breckpot Karine, Escors David
Division of Infection and Immunity. Rayne Institute. University College London. 5 University Street. WC1E 6JF. London. United Kingdom.
Immunol Endocr Metab Agents Med Chem. 2012 Sep;12(3):224-235. doi: 10.2174/187152212802001875.
One of the key roles of the immune system is the identification of potentially dangerous pathogens or tumour cells, and raising a wide range of mechanisms to eliminate them from the organism. One of these mechanisms is activation and expansion of antigen-specific cytotoxic T cells, after recognition of antigenic peptides on the surface of antigen presenting cells such as dendritic cells (DCs). However, DCs also process and present autoantigens. Therefore, antigen presentation has to occur in the appropriate context to either trigger immune responses or establishing immunological tolerance. This is achieved by co-stimulation of T cells during antigen presentation. Co-stimulation consists on the simultaneous binding of ligand-receptor molecules at the immunological synapse which will determine the type and extent of T cell responses. In addition, the type of cytokines/chemokines present during antigen presentation will influence the polarisation of T cell responses, whether they lead to tolerance, antibody responses or cytotoxicity. In this review, we will focus on approaches manipulating co-stimulation during antigen presentation, and the role of cytokine stimulation on effective T cell responses. More specifically, we will address the experimental strategies to interfere with negative co-stimulation such as that mediated by PD-L1 (Programmed cell death 1 ligand 1)/PD-1 (Programmed death 1) to enhance anti-tumour immunity.
免疫系统的关键作用之一是识别潜在危险的病原体或肿瘤细胞，并启动多种机制将它们从机体中清除。其中一种机制是在识别抗原呈递细胞（如树突状细胞，DC）表面的抗原肽后，激活并扩增抗原特异性细胞毒性T细胞。然而，DC也会处理和呈递自身抗原。因此，抗原呈递必须在适当的背景下发生，以触发免疫反应或建立免疫耐受。这是通过抗原呈递过程中对T细胞的共刺激来实现的。共刺激包括配体-受体分子在免疫突触处的同时结合，这将决定T细胞反应的类型和程度。此外，抗原呈递过程中存在的细胞因子/趋化因子类型将影响T细胞反应的极化，即它们是否导致耐受、抗体反应或细胞毒性。在本综述中，我们将重点关注在抗原呈递过程中操纵共刺激的方法，以及细胞因子刺激对有效的T细胞反应的作用。更具体地说，我们将探讨干扰负性共刺激（如由程序性细胞死亡1配体1/程序性死亡1，PD-L1/PD-1介导的负性共刺激）以增强抗肿瘤免疫力的实验策略。
