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.
|Titolo:||Ionizing radiation induces morphological changes and immunological modulation of Jurkat cells|
|Parole Chiave:||Jurkat cells; Peripheral blood lymphocytes; Radiation-induced increase in cell size; T-cell adhesion; X-ray stimulated integrin-β clustering; X-ray triggered immune stimulation; Immunology and Allergy; Immunology|
|Settore Scientifico Disciplinare:||Settore BIO/04 - Fisiologia Vegetale|
Settore BIO/09 - Fisiologia
|Data di pubblicazione:||apr-2018|
|Digital Object Identifier (DOI):||10.3389/fimmu.2018.00922|
|Appare nelle tipologie:||01 - Articolo su periodico|