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Enhancement of T cell responses as a result of synergy between lower doses of radiation and T cell stimulation

Spary, Lisa Kate, Al-Taei, Saly, Salimu, Josephine, Cook, Alexander, Ager, Ann, Watson, Heulwen Angharad, Clayton, Aled, Staffurth, John Nicholas, Mason, Malcolm David and Tabi, Zsuzsanna 2014. Enhancement of T cell responses as a result of synergy between lower doses of radiation and T cell stimulation. The Journal of Immunology 192 (7) , pp. 3101-3110. 10.4049/jimmunol.1302736

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Abstract

As a side effect of cancer radiotherapy, immune cells receive varying doses of radiation. Whereas high doses of radiation (>10 Gy) can lead to lymphopenia, lower radiation doses (2–4 Gy) represent a valid treatment option in some hematological cancers, triggering clinically relevant immunological changes. Based on our earlier observations, we hypothesized that lower radiation doses have a direct positive effect on T cells. In this study, we show that 0.6–2.4 Gy radiation enhances proliferation and IFN-γ production of PBMC or purified T cells induced by stimulation via the TCR. Radiation with 1.2 Gy also lowered T cell activation threshold and broadened the Th1 cytokine profile. Although radiation alone did not activate T cells, when followed by TCR stimulation, ERK1/2 and Akt phosphorylation increased above that induced by stimulation alone. These changes were followed by an early increase in glucose uptake. Naive (CD45RA+) or memory (CD45RA−) T cell responses to stimulation were boosted at similar rates by radiation. Whereas increased Ag-specific cytotoxic activity of a CD8+ T cell line manifested in a 4-h assay (10–20% increase), highly significant (5- to 10-fold) differences in cytokine production were detected in 6-d Ag-stimulation assays of PBMC, probably as a net outcome of death of nonstimulated and enhanced response of Ag-stimulated T cells. T cells from patients receiving pelvic radiation (2.2–2.75 Gy) also displayed increased cytokine production when stimulated in vitro. We report in this study enhanced T cell function induced by synergistic radiation treatment, with potential physiological significance in a wide range of T cell responses.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Publisher: American Association of Immunologists
ISSN: 0022-1767
Last Modified: 05 Feb 2019 17:03
URI: http://orca-mwe.cf.ac.uk/id/eprint/65772

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