Abstract:
:Impairment or stimulation of the immune system by ionizing radiation (IR) impacts on immune surveillance of tumor cells and non-malignant cells and can either foster therapy response or side effects/toxicities of radiation therapy. For a better understanding of the mechanisms by which IR modulates T-cell activation and alters functional properties of these immune cells, we exposed human immortalized Jurkat cells and peripheral blood lymphocytes (PBL) to X-ray doses between 0.1 and 5 Gy. This resulted in cellular responses, which are typically observed also in naïve T-lymphocytes in response of T-cell receptor immune stimulation or mitogens. These responses include oscillations of cytosolic Ca2+, an upregulation of CD25 surface expression, interleukin-2 and interferon-γ synthesis, elevated expression of Ca2+ sensitive K+ channels and an increase in cell diameter. The latter was sensitive to inhibition by the immunosuppressant cyclosporine A, Ca2+ buffer BAPTA-AM, and the CDK1-inhibitor RO3306, indicating the involvement of Ca2+-dependent immune activation and radiation-induced cell cycle arrest. Furthermore, on a functional level, Jurkat and PBL cell adhesion to endothelial cells was increased upon radiation exposure and was highly dependent on an upregulation of integrin beta-1 expression and clustering. In conclusion, we here report that IR impacts on immune activation and functional properties of T-lymphocytes that may have implications in both toxic effects and treatment response to combined radiation and immune therapy in cancer patients.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Voos P,Fuck S,Weipert F,Babel L,Tandl D,Meckel T,Hehlgans S,Fournier C,Moroni A,Rödel F,Thiel Gdoi
10.3389/fimmu.2018.00922subject
Has Abstractpub_date
2018-04-30 00:00:00pages
922issn
1664-3224journal_volume
9pub_type
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journal_title:Frontiers in immunology
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pub_type: 杂志文章
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abstract::[This corrects the article DOI: 10.3389/fimmu.2019.01135.]. ...
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pub_type: 已发布勘误
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pub_type: 临床试验,杂志文章
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pub_type: 杂志文章
doi:10.3389/fimmu.2014.00430
更新日期:2014-09-08 00:00:00
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doi:10.3389/fimmu.2020.602482
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