Induction of Antitumor Immune Response by Homeostatic Proliferation and CD28 Signaling
Induction of Antitumor Immune Response by Homeostatic Proliferation and CD28 Signaling
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通过稳态增殖和 CD28 信号传导诱导抗肿瘤免疫反应
DOI：
10.4049/jimmunol.180.7.4596
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
H. Kishimoto
中科院分区：
文献类型：
--
作者：
Toshihiro Suzuki;S. Ogawa;K. Tanabe;H. Tahara;R. Abe;H. Kishimoto
在过继细胞移植前诱导淋巴细胞减少可以提高供者免疫细胞的抗肿瘤效果。最近有报道称，淋巴细胞减少的条件可以启动初始T细胞向效应细胞的分化。尽管T细胞在抗原驱动的分化过程中需要通过TCR的特殊“强”信号以及共刺激信号，但几乎没有证据表明在淋巴细胞减少的宿主中，原始T细胞的分化需要共刺激信号。在这项研究中，我们证明了初始CD8+T细胞在诱导抗肿瘤效应中是必不可少的，并且，除了抗原驱动的分化外，CD28信号对于在体内平衡增殖(HP)过程中初始CD8+T细胞分化为功能效应CTL是必不可少的。在缺乏CD28信号的情况下，全身应用IL-2不能恢复幽门螺杆菌的抗肿瘤作用。这些结果表明，动态平衡细胞因子使CD8+T细胞能够扩张和存活，TCR和CD28信号启动了效应器功能的分化。深入了解幽门螺杆菌增强诱导抗肿瘤免疫反应的机制可能会使我们能够更准确地通过共刺激信号和共同的γ链细胞因子来诱导增强免疫。
Inducing lymphopenia before adoptive cell transfer can improve the antitumor effect of donor immune cells. It was recently reported that lymphopenic conditions can initiate the differentiation of naive T cells into effector cells. Although T cells require a specific “strong” signal via TCR as well as costimulatory signals during Ag-driven differentiation, there has been little evidence to suggest any requirement for costimulatory signaling for the differentiation of naive T cells in a lymphopenic host. In this study, we demonstrate that naive CD8+ T cells are indispensable for induction of antitumor effect, and, in addition to Ag-driven differentiation, CD28 signaling is essential for the differentiation of naive CD8+ T cells into functional effector CTLs during homeostatic proliferation (HP). The systemic administration of IL-2 did not restore the antitumor effect induced by HP in the absence of CD28 signaling. These results suggest that homeostatic cytokines enable CD8+ T cells to expand and survive, and that TCR and the CD28 signal initiate the differentiation of effector functions. A deeper understanding of the mechanisms underlying enhanced induction of the antitumor immune response with accompanying HP may allow us to more precisely induce enhanced immunity with costimulation signaling and the administration of common γ-chain cytokines.
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淋巴清除小鼠中黑色素瘤特异性 T 细胞依赖白介素 7 的扩增和持续存在导致肿瘤消退和编辑
影响因子：
11.2
作者：
Wang, LX;Li, R;Hu, HM
通讯作者：
Hu, HM
DOI：
10.1073/pnas.90.14.6586
发表时间：
1993-07-15
影响因子：
11.1
作者：
GIMMI, CD;FREEMAN, GJ;NADLER, LM
通讯作者：
NADLER, LM
影响因子：
56.9
作者：
Ku, CC;Murakami, M;Marrack, P
通讯作者：
Marrack, P
通过体内引发和体外致敏产生的淋巴细胞显示出对缺乏明显免疫原性的小鼠肿瘤的治疗功效。
DOI：
--
发表时间：
1989
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Shu,SY;Chou,T;Sakai,K
通讯作者：
Sakai,K