Department of Microbiology and Immunology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA; Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Trends Immunol. 2023 Sep;44(9):693-700. doi: 10.1016/j.it.2023.07.005. Epub 2023 Aug 7.
CD8 cytotoxic T lymphocytes (CTLs) play a crucial role in targeting virus-infected and cancer cells. Although other cytotoxic lymphocytes such as CD4 T and natural killer (NK) cells, as well as chimeric antigen receptor (CAR)-T cells, can also identify and destroy aberrant cells, they seem to be significantly less potent based on available experimental data. Here, I contemplate the molecular mechanisms controlling the sensitivity and kinetics of granule-mediated CD8 T cell cytolytic responses. I posit that the clustering of MHC-I molecules and T cell receptors (TCRs) on the cell surface, as well as the contribution of the CD8 co-receptor, are major factors driving exceptionally potent cytolytic responses. I also contend that CD8 T cells with known specificity and engineered TCR-T cells might be among the most efficient cytolytic effectors for treating patients suffering from viral infections or cancer.
CD8 细胞毒性 T 淋巴细胞 (CTLs) 在靶向病毒感染细胞和癌细胞方面发挥着至关重要的作用。尽管其他细胞毒性淋巴细胞,如 CD4 T 细胞和自然杀伤 (NK) 细胞,以及嵌合抗原受体 (CAR)-T 细胞,也可以识别和破坏异常细胞,但根据现有实验数据,它们的效力似乎明显较低。在这里,我思考了控制颗粒介导的 CD8 T 细胞细胞毒性反应的敏感性和动力学的分子机制。我假设 MHC-I 分子和 T 细胞受体 (TCRs) 在细胞表面上的聚类,以及 CD8 共受体的贡献,是驱动异常高效细胞毒性反应的主要因素。我还认为,具有已知特异性的 CD8 T 细胞和经过工程改造的 TCR-T 细胞可能是治疗病毒感染或癌症患者的最有效细胞毒性效应物之一。