Cited by 101Cell death mechanisms and regulationT-cell and B-cell ImmunologyRedox biology and oxidative stress

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Preferential Cell Death of CD8+ Effector Memory (CCR7−CD45RA−) T Cells by Hydrogen Peroxide-Induced Oxidative Stress

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Takahashi, Akihiro, Hanson, Mikael G V, Norell, Håkan R, Havelka, Aleksandra Mandic, Kono, Koji, Malmberg, Karl-Johan, Kiessling, Rolf V R·2005·The Journal of Immunology

DOI 10.4049/jimmunol.174.10.6080

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Abstract

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 T cell function. In this study, we have investigated the sensitivity of different human T cell subsets to H2O2-induced oxidative stress. We showed that central memory (CD45RA−CCR7+) and effector memory (CD45RA−CCR7−) T cells are more sensitive to H2O2 as compared with naive (CD45RA+CCR7+) T cells. Furthermore, the study showed that CD8+ effector memory T cells are more sensitive to low levels of H2O2 (5 μM) compared with other types of T cells investigated. H2O2-exposed CD45RO+ T cells showed mitochondrial depolarization prior to caspase 3 activity. Moreover, the pan-caspase inhibitor z-Val-Ala-Asp(OMe)-fluoromethylketone rescued cells from death. These experiments suggest that H2O2-induced cell death of CD45RO+ T cells acts via the mitochondrial pathway and that caspase involvement is needed. This study suggests that oxidative stress in cancer patients can be disadvantageous for T cell-based adoptive cell transfer therapies, since effector memory T cells are the primary phenotype of the cells administered.

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Authors: Takahashi, A., Hanson, M. G. V., Norell, H. R., Havelka, A. M., Kono, K., Malmberg, K.-J., & Kiessling, R. V. R.
Affiliations: Karolinska Institutet (SE)
Department of Oncology and Pathology, Immune and Gene Therapy Laboratory, Cancer Center Karolinska, Karolinska Institutet , Stockholm ,
University of Yamanashi (JP)
Karolinska University Hospital (SE)
Corresponding author: Takahashi, Akihiro
ORCID: Takahashi, Akihiro
Kono, Koji
Malmberg, Karl-Johan
Venue: The Journal of Immunology
Publisher: Oxford University Press (OUP)
Published: 2005-05
Volume: 174
Issue: 10
Pages: 6080-6087
ISSN: 0022-1767 (ISSN-L)
1550-6606
DOI: 10.4049/jimmunol.174.10.6080
OpenAlex: W2139536543
Cited by: 101
References: 62
Citations by year: 2026: 2 · 2025: 4 · 2024: 9 · 2023: 3 · 2022: 4 · 2021: 8 · 2020: 5 · 2019: 3 · 2018: 6 · 2017: 3 · 2016: 7 · 2015: 4 · 2014: 5 · 2013: 9 · 2012: 8
FWCI: 1.38
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: academic.oup.com/pages/standard-publication-reuse-rights (vor)
Locations: The Journal of Immunology (publishedVersion)
PubMed (publishedVersion)
Funders: European Commission
Cancerfonden
Karolinska Institutet
National Institutes of Health
National Cancer Institute (R01CA102280, CA 102280)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords: hydrogen peroxide, oxidative stress, T cell death, CD8+ effector memory T cells, central memory T cells, naive T cells, mitochondrial depolarization, caspase-3, z-VAD-fmk, adoptive cell transfer, T cell subsets, cancer immunotherapy
MeSH terms: Amino Acid Chloromethyl Ketones, Cells, Cultured, Cytotoxicity, Immunologic, Dose-Response Relationship, Immunologic, Growth Inhibitors, Humans, Hydrogen Peroxide, Immunologic Memory, Intracellular Membranes, Membrane Potentials, Mitochondria, Permeability, T-Lymphocytes, Cytotoxic, Cell Death, Leukocyte Common Antigens, Oxidative Stress, Receptors, Chemokine, Receptors, CCR7, Caspase Inhibitors

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Preferential Cell Death of CD8+ Effector Memory (CCR7−CD45RA−) T Cells by Hydrogen Peroxide-Induced Oxidative Stress

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