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Ionizing Radiation Induces Morphological Changes and Immunological Modulation of Jurkat Cells
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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5936756/ https://www.ncbi.nlm.nih.gov/pubmed/29760710 http://dx.doi.org/10.3389/fimmu.2018.00922 |
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author | Voos, Patrick Fuck, Sebastian Weipert, Fabian Babel, Laura Tandl, Dominique Meckel, Tobias Hehlgans, Stephanie Fournier, Claudia Moroni, Anna Rödel, Franz Thiel, Gerhard |
author_facet | Voos, Patrick Fuck, Sebastian Weipert, Fabian Babel, Laura Tandl, Dominique Meckel, Tobias Hehlgans, Stephanie Fournier, Claudia Moroni, Anna Rödel, Franz Thiel, Gerhard |
author_sort | Voos, Patrick |
collection | PubMed |
description | 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 Ca(2+), an upregulation of CD25 surface expression, interleukin-2 and interferon-γ synthesis, elevated expression of Ca(2+) sensitive K(+) channels and an increase in cell diameter. The latter was sensitive to inhibition by the immunosuppressant cyclosporine A, Ca(2+) buffer BAPTA-AM, and the CDK1-inhibitor RO3306, indicating the involvement of Ca(2+)-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. |
format | Online Article Text |
id | pubmed-5936756 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-59367562018-05-14 Ionizing Radiation Induces Morphological Changes and Immunological Modulation of Jurkat Cells Voos, Patrick Fuck, Sebastian Weipert, Fabian Babel, Laura Tandl, Dominique Meckel, Tobias Hehlgans, Stephanie Fournier, Claudia Moroni, Anna Rödel, Franz Thiel, Gerhard Front Immunol Immunology 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 Ca(2+), an upregulation of CD25 surface expression, interleukin-2 and interferon-γ synthesis, elevated expression of Ca(2+) sensitive K(+) channels and an increase in cell diameter. The latter was sensitive to inhibition by the immunosuppressant cyclosporine A, Ca(2+) buffer BAPTA-AM, and the CDK1-inhibitor RO3306, indicating the involvement of Ca(2+)-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. Frontiers Media S.A. 2018-04-30 /pmc/articles/PMC5936756/ /pubmed/29760710 http://dx.doi.org/10.3389/fimmu.2018.00922 Text en Copyright © 2018 Voos, Fuck, Weipert, Babel, Tandl, Meckel, Hehlgans, Fournier, Moroni, Rödel and Thiel. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Voos, Patrick Fuck, Sebastian Weipert, Fabian Babel, Laura Tandl, Dominique Meckel, Tobias Hehlgans, Stephanie Fournier, Claudia Moroni, Anna Rödel, Franz Thiel, Gerhard Ionizing Radiation Induces Morphological Changes and Immunological Modulation of Jurkat Cells |
title | Ionizing Radiation Induces Morphological Changes and Immunological Modulation of Jurkat Cells |
title_full | Ionizing Radiation Induces Morphological Changes and Immunological Modulation of Jurkat Cells |
title_fullStr | Ionizing Radiation Induces Morphological Changes and Immunological Modulation of Jurkat Cells |
title_full_unstemmed | Ionizing Radiation Induces Morphological Changes and Immunological Modulation of Jurkat Cells |
title_short | Ionizing Radiation Induces Morphological Changes and Immunological Modulation of Jurkat Cells |
title_sort | ionizing radiation induces morphological changes and immunological modulation of jurkat cells |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5936756/ https://www.ncbi.nlm.nih.gov/pubmed/29760710 http://dx.doi.org/10.3389/fimmu.2018.00922 |
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