Department of Immunology, Shanghai Medical College,Institute for Immunobiology, Key Laboratory of Molecular Medicine of Ministryof Education, Fudan University, Shanghai, China.
Cell Mol Immunol. 2010 Mar;7(2):157-62. doi: 10.1038/cmi.2009.117. Epub 2010 Feb 8.
Low-dose total body irradiation (LTBI) is used in the treatment of some cancers mainly for immune enhancement rather than cell killing. However, the mechanism underlying LTBI remains unknown. In this study, by analyzing the immune patterns of lymphocytes, we found that the percentage and absolute number of CD4(+)CD25(+)Foxp3(+) regulatory T cells are markedly decreased in naive mice following treatment with LTBI. On the contrary, the CD4(+)CD44(+)/CD8(+)CD44(+) effect or-memory T cells are greatly increased. Importantly, naive mice treated with dendritic cell-gp 100 tumor vaccines under LTBI induced an enhancement of antigen-specific proliferation and cytotoxicity as well as interferon-gamma (IFN-gamma) secretion against F10 melanoma tumor challenge, compared to treatment with either the tumor vaccine or LTBI alone. Consequently, the treatment resulted in a reduced tumor burden and prolonged mouse survival. Our data demonstrate that LTBI's enhancement of antitumor immunity was mainly associated with selectively decreasing the proportion and number of T regulatory cells,implying the potential application of the combination of LTBI and a tumor vaccine in antitumor therapy.
低剂量全身照射（LTBI）主要用于治疗某些癌症，用于增强免疫而非杀伤细胞。然而，LTBI 的作用机制尚不清楚。在这项研究中，通过分析淋巴细胞的免疫模式，我们发现 LTBI 处理后的幼稚小鼠 CD4(+)CD25(+)Foxp3(+)调节性 T 细胞的比例和绝对数量明显下降。相反，CD4(+)CD44(+)/CD8(+)CD44(+)效应或记忆 T 细胞显著增加。重要的是，在 LTBI 下用树突状细胞-gp100 肿瘤疫苗处理的幼稚小鼠在 F10 黑色素瘤肿瘤攻击时，针对抗原的特异性增殖、细胞毒性以及干扰素-γ（IFN-γ）分泌得到增强，与单独使用肿瘤疫苗或 LTBI 相比。结果，治疗导致肿瘤负担减轻和小鼠存活时间延长。我们的数据表明，LTBI 增强抗肿瘤免疫主要与选择性降低 T 调节细胞的比例和数量有关，提示 LTBI 与肿瘤疫苗联合应用于抗肿瘤治疗的潜力。
