Suzuki Toshihiro, Kishimoto Hidehiro, Abe Ryo
Division of Immunobiology, Research Institute for Biomedical Sciences, Tokyo University of Science, 2669 Yamazaki, Noda, Chiba, 278-0022, Japan.
Parasitology and Immunopathoetiology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan.
Cancer Immunol Immunother. 2016 Mar;65(3):341-54. doi: 10.1007/s00262-016-1808-7. Epub 2016 Feb 15.
Induction of lymphopenia before adoptive transfer of T cells was followed by lymphopenia-induced proliferation (LIP) and generated a potent anti-tumor immune response in rodents and in a clinical setting. Previously, we reported that CD28 signaling is essential for the differentiation of functional effector cytotoxic T lymphocytes (CTLs) under lymphopenic conditions and sequential LIP of T cells. In this study, to clarify the correlation between LIP and the anti-tumor effect, LIP was inhibited with interleukin 7 (IL7) receptor blockade at various stages, and the anti-tumor effect then assessed. We confirmed that IL7 signaling at the start of LIP is crucial for the anti-tumor immune response. In contrast, continuous IL7 signaling was not required for tumor regression, although LIP of naïve CD8+ T cells is usually regulated by IL7. The expansion and migration of CTLs in lymphopenic hosts depend on IL7 signaling during the induction phase. Here, we propose that IL7 signaling and subsequent LIP of T cells have distinct roles in the induction of T cell immunity during lymphopenia.
在T细胞过继转移前诱导淋巴细胞减少，随后出现淋巴细胞减少诱导的增殖（LIP），并在啮齿动物和临床环境中产生有效的抗肿瘤免疫反应。此前，我们报道CD28信号对于淋巴细胞减少条件下功能性效应细胞毒性T淋巴细胞（CTL）的分化以及T细胞的序贯LIP至关重要。在本研究中，为了阐明LIP与抗肿瘤效应之间的相关性，在不同阶段用白细胞介素7（IL7）受体阻断抑制LIP，然后评估抗肿瘤效应。我们证实LIP开始时的IL7信号对于抗肿瘤免疫反应至关重要。相比之下，尽管初始CD8+T细胞的LIP通常受IL7调节，但肿瘤消退并不需要持续的IL7信号。在淋巴细胞减少的宿主中，CTL的扩增和迁移在诱导阶段依赖于IL7信号。在此，我们提出IL7信号及随后的T细胞LIP在淋巴细胞减少期间T细胞免疫的诱导中具有不同作用。
