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Ionizing radiation reduces the capacity of activated macrophages to induce T-cell proliferation, but does not trigger dendritic cell-mediated non-targeted effects

Version 2 2018-08-21, 22:52
Version 1 2018-06-18, 20:41
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posted on 2018-08-21, 22:52 authored by Roland Wunderlich, Paul Friedrich Rühle, Lisa Deloch, Franz Rödel, Rainer Fietkau, Udo S. Gaipl, Benjamin Frey

Purpose: Previous investigations revealed influences of irradiation up to 2Gy on the cytokine secretion profile of inflammatory and peritoneal mouse macrophages (pMФ). This raised the question if those alterations impact on dendritic cells and consecutive T-cell responses. Further, the impact of irradiation directly on pMФ capacity to induce T-cell responses was analyzed.

Materials and methods: pMФ were LPS-activated, irradiated and the expression of activation markers was assessed. Treated pMФ were co-incubated with T-cells to investigate proliferation. To verify modulating properties of pMФ supernatants isolated 24 h after irradiation, bone marrow-derived dendritic cells (BMDC) were co-incubated with supernatants and activation markers as well as the BMDC-induced proliferation of T-cells were measured.

Results: pMФ showed a highly significantly decreased major histocompatibility complexII (MHCII) expression within a dose range from 0.7–2Gy. Further, the proliferation rate of cluster of differentiation 4+ (CD4+) T-cells was decreased after co-incubation particularly with 2 Gy irradiated pMФ. The co-incubation of BMDC with supernatants of activated, irradiated pMФ significantly reduced the CD40 expression, but did not impact on the BMDC-derived induction of T-cell proliferation.

Conclusions: Inflammatory macrophages being exposed to irradiation have the potential to modulate consecutive adaptive immune reactions. But supernatants of irradiated macrophages do not influence the dendritic cells (DC)-mediated induction of T cell proliferation.

Funding

This work was supported by the European Commission [DoReMi, European Network of Excellence, contract number 249689] and German Federal Ministry of Education and Research [GREWIS, 02NUK017G].

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