Hung K, Hayashi R, Lafond-Walker A, Lowenstein C, Pardoll D, Levitsky H
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
J Exp Med. 1998 Dec 21;188(12):2357-68. doi: 10.1084/jem.188.12.2357.
The induction of optimal systemic antitumor immunity involves the priming of both CD4(+) and CD8(+) T cells specific for tumor-associated antigens. The role of CD4(+) T helper cells (Th) in this response has been largely attributed to providing regulatory signals required for the priming of major histocompatibility complex class I restricted CD8(+) cytolytic T lymphocytes, which are thought to serve as the dominant effector cell mediating tumor killing. However, analysis of the effector phase of tumor rejection induced by vaccination with irradiated tumor cells transduced to secrete granulocyte/macrophage colony-stimulating factor indicates a far broader role for CD4(+) T cells in orchestrating the host response to tumor. This form of immunization leads to the simultaneous induction of Th1 and Th2 responses, both of which are required for maximal systemic antitumor immunity. Cytokines produced by these CD4(+) T cells activate eosinophils as well as macrophages that produce both superoxide and nitric oxide. Both of these cell types then collaborate within the site of tumor challenge to cause its destruction.
诱导最佳的全身抗肿瘤免疫反应涉及激活针对肿瘤相关抗原的CD4(+)和CD8(+) T细胞。CD4(+)辅助性T细胞（Th）在这种反应中的作用主要是为主要组织相容性复合体I类限制性CD8(+)细胞毒性T淋巴细胞的激活提供所需的调节信号，而这些CD8(+)细胞毒性T淋巴细胞被认为是介导肿瘤杀伤的主要效应细胞。然而，对经转导分泌粒细胞/巨噬细胞集落刺激因子的辐照肿瘤细胞进行疫苗接种所诱导的肿瘤排斥效应阶段的分析表明，CD4(+) T细胞在协调宿主对肿瘤的反应中发挥着更为广泛的作用。这种免疫形式会同时诱导Th1和Th2反应，这两种反应对于最大程度的全身抗肿瘤免疫都是必需的。这些CD4(+) T细胞产生的细胞因子会激活嗜酸性粒细胞以及产生超氧化物和一氧化氮的巨噬细胞。然后，这两种细胞类型在肿瘤攻击部位协同作用，导致肿瘤被破坏。
