Influence of low dose irradiation on differentiation, maturation and T-cell activation of human dendritic cells

Department of Radiotherapy and Radiation Oncology, University of Leipzig, Stephanstrasse 21, 04103 Leipzig, Germany.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis (Impact Factor: 3.68). 03/2011; 709-710:32-9. DOI: 10.1016/j.mrfmmm.2011.02.007
Source: PubMed


Ionizing irradiation could act directly on immune cells and may induce bystander effects mediated by soluble factors that are released by the irradiated cells. This is the first study analyzing both the direct effect of low dose ionizing radiation (LDIR) on the maturation and cytokine release of human dendritic cells (DCs) and the functional consequences for co-cultured T-cells. We showed that irradiation of DC-precursors in vitro does not influence surface marker expression or cytokine profile of immature DCs nor of mature DCs after LPS treatment. There was no difference of single dose irradiation versus fractionated irradiation protocols on the behavior of the mature DCs. Further, the low dose irradiation did not change the capacity of the DCs to stimulate T-cell proliferation. But the irradiation of the co-culture of DCs and T-cells revealed significantly lower proliferation of T-cells with higher doses. Summarizing the data from approx. 50 DC preparations there is no significant effect of low dose ionizing irradiation on the cytokine profile, surface marker expression and maturation of DCs in vitro although functional consequences cannot be excluded.

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Available from: Ulf Anderegg, Oct 05, 2015
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    • "In fact, long-term accumulative radiation dose (<1 Gy) appears to enhance the resilience and tolerance of cells. It was observed that, under such a condition, even though T lymphocyte proliferation was inhibited, the innate immune system and naive T cell differentiation were activated and immune functions were enhanced, while the activity and maturation of dendritic cells were unaffected [9] [15] [16]. These findings also suggest that sensitivity and tolerance to radiation are different among the variety of immune cells in the body. "
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    ABSTRACT: Though damage caused by radiation has been the focus of rigorous research, the mechanisms through which radiation exerts harmful effects on cells are complex and not well-understood. In particular, the influence of low dose radiation exposure on the regulation of genes and pathways remains unclear. In an attempt to investigate the molecular alterations induced by varying doses of radiation, a genome-wide expression analysis was conducted. Peripheral blood mononuclear cells were collected from five participants and each sample was subjected to 0.5 Gy, 1 Gy, 2.5 Gy, and 5 Gy of cobalt 60 radiation, followed by array-based expression profiling. Gene set enrichment analysis indicated that the immune system and cancer development pathways appeared to be the major affected targets by radiation exposure. Therefore, 1 Gy radioactive exposure seemed to be a critical threshold dosage. In fact, after 1 Gy radiation exposure, expression levels of several genes including FADD, TNFRSF10B, TNFRSF8, TNFRSF10A, TNFSF10, TNFSF8, CASP1, and CASP4 that are associated with carcinogenesis and metabolic disorders showed significant alterations. Our results suggest that exposure to low-dose radiation may elicit changes in metabolic and immune pathways, potentially increasing the risk of immune dysfunctions and metabolic disorders.
    BioMed Research International 09/2014; 2014:834087. DOI:10.1155/2014/834087 · 2.71 Impact Factor
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    • "CD86 (B7.2), and HLA-DR on the DC. On the other hand, Jahns et al. (2011) studied ex vivo preparations of leukocytes, focusing on quantitative functional impact on DC versus the impact onto lymphocytes. They found that DC are less sensitive to apoptosis than lymphocytes, and maintained the same functional level (in terms of cytokine profiles, surface markers , and maturation) after a radiation dose that impaired T cell function. "
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    ABSTRACT: Preclinical work in murine models suggests that local radiotherapy plus intratumoral syngeneic dendritic cells (DC) injection can mediate immunologic tumor eradication. Radiotherapy affects the immune response to cancer, besides the direct impact on the tumor cells, and other ways to coordinate immune modulation with radiotherapy have been explored. We review here the potential for immune-mediated anticancer activity of radiation on tumors. This can be mediated by differential antigen acquisition and presentation by DC, through changes of lymphocytes' activation, and changes of tumor susceptibility to immune clearance. Recent work has implemented the combination of external beam radiation therapy (EBRT) with intratumoral injection of DC. This included a pilot study of coordinated intraprostatic, autologous DC injection together with radiation therapy with five HLA-A2(+) subjects with high-risk, localized prostate cancer; the protocol used androgen suppression, EBRT (25 fractions, 45 Gy), DC injections after fractions 5, 15, and 25, and then interstitial radioactive implant. Another was a phase II trial using neo-adjuvant apoptosis-inducing EBRT plus intra-tumoral DC in soft tissue sarcoma, to test if this would increase immune activity toward soft tissue sarcoma associated antigens. In the future, radiation therapy approaches designed to optimize immune stimulation at the level of DC, lymphocytes, tumor and stroma effects could be evaluated specifically in clinical trials.
    Frontiers in Oncology 11/2012; 2:169. DOI:10.3389/fonc.2012.00169
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    • "Finally, Jahns et al. recently analyzed the effect of LD-RT on the maturation, cytokine release, and T-Lymphocyte activation of human DCs. They indicated that irradiation of DC-precursors in vitro does not influence surface marker (CD80, CD83, CD86) expression or cytokine profile of immature DCs nor of mature DCs stimulated by LPS, neither did it influence the capacity of the DCs to stimulate T-cell proliferation (Jahns et al., 2011). "
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    ABSTRACT: Inflammatory diseases are the result of complex and pathologically unbalanced multicellular interactions. For decades, low-dose X-irradiation therapy (LD-RT) has been clinically documented to exert an anti-inflammatory effect on benign diseases and chronic degenerative disorders. By contrast, experimental studies to confirm the effectiveness and to reveal underlying cellular and molecular mechanisms are still at their early stages. During the last decade, however, the modulation of a multitude of immunological processes by LD-RT has been explored in vitro and in vivo. These include leukocyte/endothelial cell adhesion, adhesion molecule and cytokine/chemokine expression, apoptosis induction, and mononuclear/polymorphonuclear cell metabolism and activity. Interestingly, these mechanisms display comparable dose dependences and dose-effect relationships with a maximum effect in the range between 0.3 and 0.7 Gy, already empirically identified to be most effective in the clinical routine. This review summarizes data and models exploring the mechanisms underlying the immunomodulatory properties of LD-RT that may serve as a prerequisite for further systematic analyses to optimize low-dose irradiation procedures in future clinical practice.
    Frontiers in Oncology 09/2012; 2:120. DOI:10.3389/fonc.2012.00120
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