Ivanova Olga K, Sharapova Tatiana N, Romanova Elena A, Soshnikova Natalia V, Sashchenko Lidia P, Yashin Denis V
Department of Molecular Immunogenetics of Cancer, Institute of Gene Biology RAS, 34/5 Vavilova str., Moscow 119334, Russia.
J Cell Biochem. 2017 Oct;118(10):3359-3366. doi: 10.1002/jcb.25990. Epub 2017 May 3.
An important problem in cellular immunology is to identify new populations of cytotoxic lymphocytes capable of killing tumor cells that have lost classical components of MHC-machinery and to understand mechanisms of the death of these cells. We have previously found that CD4 CD25 lymphocytes appear in the lymphokine-activated killer (LAK) cell culture, which carry Tag7 (PGRP-S) and FasL proteins on their surface and can kill Hsp70- and Fas-expressing HLA-negative cells. In this work, we have continued to study the mechanisms of killing of the HLA-negative tumor cells, focusing this time on the CD8 lymphocytes. We show that after a tumor antigen contact the IL-2 activated CD8 lymphocytes acquire ability to lyse tumor cells bearing this antigen. However, activation of the CD8 lymphocytes in the absence of antigen causes appearance of a cytotoxic population of CD8 NKG2D lymphocytes, which are able to lyse HLA-negative cancer cells that have lost the classic mechanism of antigen presentation. These cells recognize the noncanonical MicA antigen on the surface of HLA-negative K562 cells but kill them via the FasL-Fas interaction, as do cytotoxic T lymphocytes. FasL presented on the lymphocyte surface can trigger both apoptosis and necroptosis. Unlike in the case of TNFR1, another cell death receptor, no switching to alternative processes has been observed upon induction of Fas-dependent cell death. It may well be that the apoptotic and necroptotic signals are transduced separately in the latter case, with the ability of FasL lymphocytes to induce necroptosis allowing them to kill tumor cells that escape apoptosis. J. Cell. Biochem. 118: 3359-3366, 2017. © 2017 Wiley Periodicals, Inc.
细胞免疫学中的一个重要问题是识别能够杀死已丧失MHC机制经典成分的肿瘤细胞的新型细胞毒性淋巴细胞群体，并了解这些细胞的死亡机制。我们之前发现，CD4 CD25淋巴细胞出现在淋巴因子激活的杀伤（LAK）细胞培养物中，它们在表面携带Tag7（PGRP-S）和FasL蛋白，并且能够杀死表达Hsp70和Fas的HLA阴性细胞。在这项工作中，我们继续研究HLA阴性肿瘤细胞的杀伤机制，这次重点关注CD8淋巴细胞。我们发现，肿瘤抗原接触后，IL-2激活的CD8淋巴细胞获得了裂解携带该抗原的肿瘤细胞的能力。然而，在没有抗原的情况下激活CD8淋巴细胞会导致出现细胞毒性的CD8 NKG2D淋巴细胞群体，它们能够裂解已丧失经典抗原呈递机制的HLA阴性癌细胞。这些细胞识别HLA阴性K562细胞表面的非经典MicA抗原，但通过FasL-Fas相互作用杀死它们，细胞毒性T淋巴细胞也是如此。淋巴细胞表面呈现的FasL既能触发凋亡也能触发坏死性凋亡。与另一种细胞死亡受体TNFR1的情况不同，在诱导Fas依赖性细胞死亡时未观察到向替代过程的转换。很可能在后者的情况下，凋亡和坏死性凋亡信号是分别转导的，FasL淋巴细胞诱导坏死性凋亡的能力使它们能够杀死逃避凋亡的肿瘤细胞。《细胞生物化学杂志》118: 3359 - 3366, 2017。© 2017威利期刊公司
