Boissonnas Alexandre, Combadiere Christophe, Lavergne Elise, Maho Maud, Blanc Catherine, Debré Patrice, Combadiere Behazine
Laboratoire d'Immunologie Cellulaire, Institut National de la Santé et de la Recherche Médicale, Unité 543, Faculté de Médecine Pitié-Salpêtrière, 91 Boulevard de l'Hôpital, 75634 Paris cedex 13, France.
J Immunol. 2004 Jul 1;173(1):222-9. doi: 10.4049/jimmunol.173.1.222.
Understanding both the role of tumor Ag in CD8 cell differentiation and the reasons that CD8 cells may work inefficiently is crucial for therapeutic approaches in cancer. We studied OT-1 CD8 cell responses in vivo in a differential Ag-distribution model that used EG-7, the EL-4 thymoma transfected with OVA. On their initial Ag encounter, OT-1 CD8 cells underwent programmed expansion in the lymph nodes, where they acquired the ability to migrate to the encapsulated tumor site after > or =4 divisions, without continuous antigenic stimulation. This short antigenic stimulation was sufficient to induce the migration differentiation program, which included modulation of chemokine receptor mRNA expression and down-regulation of CD62L. Moreover, Ag quantity determined the behavior of the OT-1 CD8 cells, including their effector functions and sensitivity to apoptosis. Thus, the initial Ag encounter drives the programmed cell migration potencies, but neither effector functions nor cell death can occur without continuous TCR triggering.
了解肿瘤抗原在CD8细胞分化中的作用以及CD8细胞可能低效工作的原因对于癌症治疗方法至关重要。我们在一个使用EG-7（转染了OVA的EL-4胸腺瘤）的差异抗原分布模型中研究了体内OT-1 CD8细胞的反应。在首次接触抗原时，OT-1 CD8细胞在淋巴结中经历程序性扩增，在≥4次分裂后获得迁移到被膜肿瘤部位的能力，且无需持续抗原刺激。这种短暂的抗原刺激足以诱导迁移分化程序，其中包括趋化因子受体mRNA表达的调节和CD62L的下调。此外，抗原数量决定了OT-1 CD8细胞的行为，包括它们的效应功能和对凋亡的敏感性。因此，首次接触抗原驱动程序性细胞迁移能力，但没有持续的TCR触发，效应功能和细胞死亡都不会发生。
