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Ionizing Radiation Induces Morphological Changes and Immunological Modulation of Jurkat Cells

Voos, Patrick and Fuck, Sebastian and Weipert, Fabian and Babel, Laura and Tandl, Dominique and Meckel, Tobias and Hehlgans, Stephanie and Fournier, Claudia and Moroni, Anna and Rödel, Franz and Thiel, Gerhard (2018):
Ionizing Radiation Induces Morphological Changes and Immunological Modulation of Jurkat Cells.
In: Frontiers in Immunology, 9, ISSN 1664-3224,
DOI: 10.3389/fimmu.2018.00922,
[Online-Edition: https://doi.org/10.3389/fimmu.2018.00922],
[Article]

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.

Item Type: Article
Erschienen: 2018
Creators: Voos, Patrick and Fuck, Sebastian and Weipert, Fabian and Babel, Laura and Tandl, Dominique and Meckel, Tobias and Hehlgans, Stephanie and Fournier, Claudia and Moroni, Anna and Rödel, Franz and Thiel, Gerhard
Title: Ionizing Radiation Induces Morphological Changes and Immunological Modulation of Jurkat Cells
Language: English
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 or Publication Title: Frontiers in Immunology
Volume: 9
Divisions: 10 Department of Biology
10 Department of Biology > Plant Membrane Biophysics
10 Department of Biology > Membrane Dynamics
Date Deposited: 03 Jun 2018 19:55
DOI: 10.3389/fimmu.2018.00922
Official URL: https://doi.org/10.3389/fimmu.2018.00922
URN: urn:nbn:de:tuda-tuprints-74493
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