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Engagement of lymphoma T cell receptors causes accelerated growth and the secretion of an NK cell-inhibitory factor
Cellular Immunology ( IF 3.7 ) Pub Date : 2020-09-11 , DOI: 10.1016/j.cellimm.2020.104213
Sigrid Dubois 1 , Thomas A Waldmann 1 , Jürgen R Müller 1
Affiliation  

The development of T cell lymphomas in mice that constitutively express a single T cell receptor is surveilled by the action of NK cells. We investigated the effects of engaging the lymphoma TCR in this mouse model. We stimulated lymphoma cells expressing an ovalbumin-specific TCR in vivo using listeria monocytogenes as a vehicle. Infections with listeria expressing ovalbumin but not with control bacteria caused a stable change in lymphoma cells that allowed its growth in mice with normal NK cells. TCR engagement furthermore enhanced lymphoma growth in NK-cell-depleted mice suggesting a lymphoma-intrinsic change that lead to accelerated growth. The ability to grow in mice without prior NK cell depletion did not appear to be accompanied by changes in the recognition of lymphoma by NK cells. Rather, lymphoma immunization was associated with a decrease in NK cell numbers: Leukemic phases were observed for all mice starting three to eight weeks after immunizations, and leukemias were succeeded by the disappearance of NK cells from blood. We also observed strong decreases of NK cell numbers in spleens at the time of death. Co-culture experiments showed decreases in the ability of NK cells to proliferate in response to IL-15 when post-immunization lymphoma cells were present in a mechanism that did not require direct cell contact. Together these data suggest that TCR engagement caused intrinsic changes in T cell lymphoma cells resulting in both accelerated in vivo growth and in the secretion of a factor that caused NK cell disappearance.



中文翻译:

淋巴瘤 T 细胞受体的参与导致加速生长和 NK 细胞抑制因子的分泌

通过 NK 细胞的作用来监测组成型表达单个 T 细胞受体的小鼠中 T 细胞淋巴瘤的发展。我们研究了在该小鼠模型中使用淋巴瘤 TCR 的影响。我们使用单核细胞增生李斯特菌作为载体刺激了体内表达卵清蛋白特异性 TCR 的淋巴瘤细胞。感染表达卵清蛋白的李斯特菌但未感染对照细菌导致淋巴瘤细胞发生稳定变化,使其在具有正常 NK 细胞的小鼠中生长。TCR 参与进一步增强了 NK 细胞耗尽小鼠的淋巴瘤生长,表明淋巴瘤内在变化导致加速生长。在没有先前 NK 细胞耗竭的小鼠中生长的能力似乎并没有伴随着 NK 细胞对淋巴瘤的识别发生变化。相当,淋巴瘤免疫与 NK 细胞数量的减少有关:在免疫后 3 至 8 周开始观察到所有小鼠的白血病阶段,并且白血病因 NK 细胞从血液中消失而成功。我们还观察到死亡时脾脏中 NK 细胞数量的强烈减少。共培养实验表明,当免疫后淋巴瘤细胞以不需要直接细胞接触的机制存在时,NK 细胞响应 IL-15 的增殖能力降低。这些数据一起表明,TCR 参与导致 T 细胞淋巴瘤细胞的内在变化,导致体内生长加速和导致 NK 细胞消失的因子的分泌。在免疫后三到八周开始观察到所有小鼠的白血病阶段,并且白血病通过血液中 NK 细胞的消失而成功。我们还观察到死亡时脾脏中 NK 细胞数量的强烈减少。共培养实验表明,当免疫后淋巴瘤细胞以不需要直接细胞接触的机制存在时,NK 细胞响应 IL-15 的增殖能力降低。这些数据一起表明,TCR 参与导致 T 细胞淋巴瘤细胞的内在变化,导致体内生长加速和导致 NK 细胞消失的因子的分泌。在免疫后三到八周开始观察到所有小鼠的白血病阶段,并且白血病通过血液中 NK 细胞的消失而成功。我们还观察到死亡时脾脏中 NK 细胞数量的强烈减少。共培养实验表明,当免疫后淋巴瘤细胞以不需要直接细胞接触的机制存在时,NK 细胞响应 IL-15 的增殖能力降低。这些数据一起表明,TCR 参与导致 T 细胞淋巴瘤细胞的内在变化,导致体内生长加速和导致 NK 细胞消失的因子的分泌。共培养实验表明,当免疫后淋巴瘤细胞以不需要直接细胞接触的机制存在时,NK 细胞响应 IL-15 的增殖能力降低。这些数据一起表明,TCR 参与导致 T 细胞淋巴瘤细胞的内在变化,导致体内生长加速和导致 NK 细胞消失的因子的分泌。共培养实验表明,当免疫后淋巴瘤细胞以不需要直接细胞接触的机制存在时,NK 细胞响应 IL-15 的增殖能力降低。这些数据一起表明,TCR 参与导致 T 细胞淋巴瘤细胞的内在变化,导致体内生长加速和导致 NK 细胞消失的因子的分泌。

更新日期:2020-09-22
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