Kaschek Lea, Zöphel Sylvia, Knörck Arne, Hoth Markus
Department of Biophysics, Center for Integrative Physiology and Molecular Medicine, Medical Faculty, Saarland University, Homburg, Germany.
Department of Biophysics, Center for Integrative Physiology and Molecular Medicine, Medical Faculty, Saarland University, Homburg, Germany.
Semin Cell Dev Biol. 2021 Jul;115:10-18. doi: 10.1016/j.semcdb.2020.12.002. Epub 2021 Jan 6.
Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells are required for host defense. They destroy malignant target cells like cancer cells. Among metal cations, Ca plays a prescinded role for CTL and NK cytotoxicity as it is the only cation used as ubiquitous second messenger. Measuring intracellular Ca concentrations [Ca] in single cells has greatly changed our understanding of Ca signaling. Yet, comparing the role of Ca in the pre-[Ca] and [Ca] measurement era reveals that even in the pre-[Ca] measurement era (before 1980), the functions of Ca and some other metal cations for the cytotoxic immune response were well established. It was even shown that Ca influx across the plasma membrane but not Ca release from intracellular sources is relevant for lymphocyte cytotoxicity and that very little Ca is needed for efficient lymphocyte cytotoxicity against cancer cells. In the [Ca] measurement era after 1980, many of the important findings were better and more quantitatively refined and in addition the molecules important for Ca transport were defined. The unexpected finding that there is a Ca optimum of CTL and NK cell cytotoxicity deserves some attention and may be important for anti-cancer therapy.
细胞毒性T淋巴细胞（CTL）和自然杀伤（NK）细胞是宿主防御所必需的。它们会破坏诸如癌细胞之类的恶性靶细胞。在金属阳离子中，钙对CTL和NK细胞毒性起着不可或缺的作用，因为它是唯一用作普遍存在的第二信使的阳离子。测量单细胞内的钙浓度[Ca]极大地改变了我们对钙信号传导的理解。然而，比较钙在[Ca]测量之前和之后的作用可以发现，即使在[Ca]测量之前的时代（1980年之前），钙和其他一些金属阳离子对细胞毒性免疫反应的作用就已经得到了充分的确立。甚至有研究表明，跨质膜的钙内流而非细胞内钙源的释放与淋巴细胞细胞毒性相关，并且高效的淋巴细胞对癌细胞的细胞毒性所需的钙量极少。在1980年之后的[Ca]测量时代，许多重要发现得到了更好、更定量的完善，此外，还确定了对钙运输重要的分子。CTL和NK细胞细胞毒性存在钙最佳值这一意外发现值得关注，可能对抗癌治疗具有重要意义。
