Systemic LPS Translocation Activates Cross-Presenting Dendritic Cells but Is Dispensable for the Breakdown of CD8+ T Cell Peripheral Tolerance in Irradiated Mice.
Systemic LPS Translocation Activates Cross-Presenting Dendritic Cells but Is Dispensable for the Breakdown of CD8+ T Cell Peripheral Tolerance in Irradiated Mice.
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DOI：
10.1371/journal.pone.0130041
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Hernandez J
中科院分区：
文献类型：
--
作者：
Espinosa-Carrasco G;Villard M;Le Saout C;Louis-Plence P;Vicente R;Hernandez J
淋巴滤除目前被用于提高细胞毒性T淋巴细胞过继转移免疫治疗抗癌的疗效。调节方案的这种有益效果至少部分归因于促进外周CD8+T细胞耐受性的崩溃。全身照射所致的淋巴枯竭可诱导胃肠道内毒素的系统性移位。由于内毒素是包括抗原提呈树突状细胞在内的天然免疫系统的有效激活剂，我们推测在辐射小鼠观察到的外周耐受性崩溃可能需要内毒素易位。为了解决这个问题，我们用抗生素治疗受辐射的小鼠，以防止内毒素易位，并将其用于T细胞过继转移实验。令人惊讶的是，我们发现，尽管完全阻断了内毒素进入血液的转位，但抗生素治疗并不能阻止外周耐受性的崩溃。虽然辐射诱导了淋巴组织中交叉递呈的CD8+树突状细胞的激活，但内毒素不能单独解释这一效应。通过内毒素易位以外的其他机制激活树突状细胞足以促进潜在的自身反应性CD8+T细胞在辐射小鼠中分化为效应者。我们的数据表明，内毒素易位在照射小鼠的CD8+T细胞耐受性的破坏中是必不可少的。
Lymphodepletion is currently used to enhance the efficacy of cytotoxic T lymphocyte adoptive transfer immunotherapy against cancer. This beneficial effect of conditioning regimens is due, at least in part, to promoting the breakdown of peripheral CD8+ T cell tolerance. Lymphodepletion by total body irradiation induces systemic translocation of commensal bacteria LPS from the gastrointestinal tract. Since LPS is a potent activator of the innate immune system, including antigen presenting dendritic cells, we hypothesized that LPS translocation could be required for the breakdown of peripheral tolerance observed in irradiated mice. To address this issue, we have treated irradiated mice with antibiotics in order to prevent LPS translocation and utilized them in T cell adoptive transfer experiments. Surprisingly, we found that despite of completely blocking LPS translocation into the bloodstream, antibiotic treatment did not prevent the breakdown of peripheral tolerance. Although irradiation induced the activation of cross-presenting CD8+ dendritic cells in the lymphoid tissue, LPS could not solely account for this effect. Activation of dendritic cells by mechanisms other than LPS translocation is sufficient to promote the differentiation of potentially autoreactive CD8+ T cells into effectors in irradiated mice. Our data indicate that LPS translocation is dispensable for the breakdown of CD8+ T cell tolerance in irradiated mice.
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影响因子：
32.4
作者：
Ernst, B;Lee, DS;Surh, CD
通讯作者：
Surh, CD
通过淋巴结消除来清除稳态细胞因子下沉，增强了采用转移的肿瘤特异性CD8+ T细胞的功效。
影响因子：
15.3
作者：
Gattinoni, Luca;Finkelstein, Steven E;Klebanoff, Christopher A;Antony, Paul A;Palmer, Douglas C;Spiess, Paul J;Hwang, Leroy N;Yu, Zhiya;Wrzesinski, Claudia;Heimann, David M;Surh, Charles D;Rosenberg, Steven A;Restifo, Nicholas P
通讯作者：
Restifo, Nicholas P
影响因子：
4.4
作者：
Hamilton-Williams, EE;Lang, A;Kurts, C
通讯作者：
Kurts, C
DOI：
10.1084/jem.192.12.1685
发表时间：
2000-12-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
den Haan JM;Lehar SM;Bevan MJ
通讯作者：
Bevan MJ
CD8α(+)树突状细胞负责诱导外周组织相关抗原的自身耐受。
影响因子：
15.3
作者：
Belz, Gabrielle T;Behrens, Georg M N;Smith, Chris M;Miller, Jacques F A P;Jones, Claerwen;Lejon, Kristina;Fathman, C Garrison;Mueller, Scott N;Shortman, Ken;Carbone, Francis R;Heath, William R
通讯作者：
Heath, William R