CD3 hyporesponsiveness and in vitro apoptosis are features of T cells from both malignant and nonmalignant secondary lymphoid organs
CD3 hyporesponsiveness and in vitro apoptosis are features of T cells from both malignant and nonmalignant secondary lymphoid organs
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DOI：
10.1172/jci3784
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发表时间：
1998-11-01
影响因子：
15.9
通讯作者：
Farcet, JP
中科院分区：
文献类型：
--
作者：
Agrawal, S;Marquet, J;Farcet, JP
肿瘤免疫学中有一个教条，肿瘤浸润淋巴细胞（TIL）是有缺陷的，这是基于它们在体内缺乏抗肿瘤功效和对体外功能测试的反应受损。然而，TIL通常与外周血T淋巴细胞进行比较，这对结论提出了质疑。因此，我们比较了来自B细胞非霍奇金淋巴瘤（NHL）的TIL和来自非恶性次级淋巴器官的T细胞。NHL-TIL对固定化抗CD3单抗的激活没有反应，尽管绕过T细胞受体(TCR)/CD3信号传导导致增殖。NHL-TU的增殖反应较差，不能用TCR zeta表达的定量缺陷来解释。NHL TIL在体外有明显的自发凋亡，培养24 h后细胞损失接近50%。这与抗凋亡Bcl-x(L)和Bcl-2蛋白的下调有关，而活的NHL-TIL维持其IL-2、抗cd3 /IL-2的表达，Fas/Fas配体死亡途径的操纵对NHL-TIL的存活没有影响。凋亡不是由于细胞周期增加，因为NHL-TIL是静止的非增殖细胞。来自炎性、非恶性组织的T细胞与NHL-TIL具有相似的功能结果，表明存在这些不同病理微环境的共同因素。因此，NHL-TIL的静止无能表型不能仅仅归因于肿瘤因素，而是来自慢性炎性病变的T细胞的特征。
There is a dogma in tumor immunology that tumor-infiltrating lymphocytes (TIL) are defective based on their lack of antitumoral efficacy in vivo and on impaired response to in vitro functional tests. However, TIL have been compared usually with peripheral blood T lymphocytes, raising doubts on the conclusions drawn. Therefore, we compared TIL from B cell non-Hodgkin's lymphomas (NHL) with T cells from nonmalignant secondary lymphoid organs. NHL-TIL were unresponsive to activation by immobilized anti-CD3 mAb, although bypassing T cell receptor (TCR)/CD3 signaling led to proliferation. The poor proliferative responses of NHL-TU, could not be explained by quantitative defects in TCR zeta expression. NHL TIL underwent marked spontaneous apoptosis in vitro with loss of similar to 50% Of cells after 24 h of culture. This was associated with downregulation of the antiapoptotic Bcl-x(L) and Bcl-2 proteins, whereas viable NHL-TIL maintained their expression IL-2, anti-CD3/IL-2, and manipulation of the Fas/Fas-ligand death pathway had no effect on NHL-TIL survival. Apoptosis was not due to increased cell cycling, as NHL-TIL were quiescent, nonproliferating cells. T cells from inflammatory, nonmalignant tissues gave similar functional results to NHL-TIL, suggesting the existence of factors common to the microenvironment of these diverse pathologies. Thus, the quiescent, anergic phenotype of NHL-TIL cannot be attributed solely to tumor factors, but rather is a feature of T cells from chronic inflammatory lesions.