Preferential Cell Death of CD8+Effector Memory (CCR7−CD45RA−) T Cells by Hydrogen Peroxide-Induced Oxidative Stress
作者： Akihiro Takahashi , Mikael G. V. Hanson , Håkan R. Norell , Aleksandra Mandic Havelka , Koji Kono
DOI: 10.4049/JIMMUNOL.174.10.6080
关键词: CD40 、 Biology 、 Interleukin 21 、 Cell biology 、 CD28 、 IL-2 receptor 、 T cell 、 Cytotoxic T cell 、 Interleukin 12 、 ZAP70 、 Immunology
摘要: T cells are used in many cell-based cancer treatments. However, oxidative stress that is induced during various chronic inflammatory conditions, such as cancer, can impair the immune system and have detrimental effects on cell function. In this study, we investigated sensitivity of different human subsets to H(2)O(2)-induced stress. We showed central memory (CD45RA(-)CCR7(+)) effector (CD45RA(-)CCR7(-)) more sensitive H(2)O(2) compared with naive (CD45RA(+)CCR7(+)) cells. Furthermore, study CD8(+) low levels (5 microM) other types investigated. H(2)O(2)-exposed CD45RO(+) mitochondrial depolarization prior caspase 3 activity. Moreover, pan-caspase inhibitor z-Val-Ala-Asp(OMe)-fluoromethylketone rescued from death. These experiments suggest death acts via pathway involvement needed. This suggests patients be disadvantageous for adoptive transfer therapies, since primary phenotype administered.
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