Low-dose Photon and Simulated Solar Particle Event Proton Effects on Foxp3<sup>+</sup>T Regulatory Cells and other Leukocytes

Gridley, Daila S.; Luo-Owen, Xian; Rizvi, Asma; Makinde, Adeola Y.; Pecaut, Michael J.; Mao, Xiao Wen; Slater, James M.

doi:10.1177/153303461000900612

Cited by 20 publications

(9 citation statements)

References 52 publications

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“…This suggests that either c rays had a minimal impact on the response to a subsequent high- dose proton exposure or that the response to 2 and 3 Gy protons overwhelmed any protective effect of the preexposure to c rays. In general, these data are consistent with our previous findings for low-dose/low-dose-rate c rays used alone or in combination with protons simulating a solar particle event (36,39).…”

Section: Discussionsupporting

confidence: 92%

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Low-Dose Total-Body γ Irradiation Modulates Immune Response to Acute Proton Radiation

et al. 2012

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Health risks due to exposure to low-dose/low-dose-rate radiation alone or when combined with acute irradiation are not yet clearly defined. This study quantified the effects of protracted exposure to low-dose/low-dose-rate γ rays with and without acute exposure to protons on the response of immune and other cell populations. C57BL/6 mice were irradiated with ⁵⁷Co (0.05 Gy at 0.025 cGy/h); subsets were subsequently exposed to high-dose/high-dose-rate proton radiation (250 MeV; 2 or 3 Gy at 0.5 Gy/min). Analyses were performed at 4 and 17 days postexposure. Spleen and thymus masses relative to body mass were decreased on day 4 after proton irradiation with or without pre-exposure to γ rays; by day 17, however, the decrease was attenuated by the priming dose. Proton dose-dependent decreases, either with or without pre-exposure to γ rays, occurred in white blood cell, lymphocyte and granulocyte counts in blood but not in spleen. A similar pattern was found for lymphocyte subpopulations, including CD3+ T, CD19+ B, CD4+ T, CD8+ T and NK1.1+ natural killer (NK) cells. Spontaneous DNA synthesis by leukocytes after proton irradiation was high in blood on day 4 and high in spleen on day 17; priming with γ radiation attenuated the effect of 3 Gy in both body compartments. Some differences were also noted among groups in erythrocyte and thrombocyte characteristics. Analysis of splenocytes activated with anti-CD3/anti-CD28 antibodies showed changes in T-helper 1 (Th1) and Th2 cytokines. Overall, the data demonstrate that pre-exposure of an intact mammal to low-dose/low-dose-rate γ rays can attenuate the response to acute exposure to proton radiation with respect to at least some cell populations.

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Section: Discussionsupporting

confidence: 92%

“…As described previously (36), the mice were c-irradiated with 57 Co plates (185 MBq activity; AEA Technology, Burlington, MA) placed directly beneath the cages (1 plate/2 cages) in a BioZone rack. A total dose of 0.05 Gy was delivered at 0.025 cGy/h over a period of approximately 8 days.…”

Section: Low-dose/low-dose-rate Photon Irradiationmentioning

confidence: 99%

Low-Dose Total-Body γ Irradiation Modulates Immune Response to Acute Proton Radiation

et al. 2012

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“…In addition, an allograft rejection that likely requires memory regulatory T cells is substantially different from a DTH response. Our study is in agreement with studies that show a relative increase in splenic regulatory T cells after irradiation [40]–[45].…”

Section: Discussionsupporting

confidence: 93%

Ionizing Radiation Selectively Reduces Skin Regulatory T Cells and Alters Immune Function

Zhou

Balint

et al. 2014

PLoS ONE

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The skin serves multiple functions that are critical for life. The protection from pathogens is achieved by a complicated interaction between aggressive effectors and controlling functions that limit damage. Inhomogeneous radiation with limited penetration is used in certain types of therapeutics and is experienced with exposure to solar particle events outside the protection of the Earth’s magnetic field. This study explores the effect of ionizing radiation on skin immune function. We demonstrate that radiation, both homogeneous and inhomogeneous, induces inflammation with resultant specific loss of regulatory T cells from the skin. This results in a hyper-responsive state with increased delayed type hypersensitivity in vivo and CD4+ T cell proliferation in vitro. The effects of inhomogeneous radiation to the skin of astronauts or as part of a therapeutic approach could result in an unexpected enhancement in skin immune function. The effects of this need to be considered in the design of radiation therapy protocols and in the development of countermeasures for extended space travel.

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“…In the context of radioprotection, previous studies investigated whether pre-exposure to radiation might have an impact on an individual's radiation sensitivity of the immune system. So far, different studies gave contradictory results [ 141 ] [ 142 ] [ 143 ] [ 144 ]. Therefore it is worthwhile to further investigate whether pre-exposure to low-dose radiation may offer some degree of radioprotection.…”

Section: Major Health Threat From Cosmic Radiationmentioning

confidence: 99%

Vive la radiorésistance!: converging research in radiobiology and biogerontology to enhance human radioresistance for deep space exploration and colonization

et al. 2018

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While many efforts have been made to pave the way toward human space colonization, little consideration has been given to the methods of protecting spacefarers against harsh cosmic and local radioactive environments and the high costs associated with protection from the deleterious physiological effects of exposure to high-Linear energy transfer (high-LET) radiation. Herein, we lay the foundations of a roadmap toward enhancing human radioresistance for the purposes of deep space colonization and exploration. We outline future research directions toward the goal of enhancing human radioresistance, including upregulation of endogenous repair and radioprotective mechanisms, possible leeways into gene therapy in order to enhance radioresistance via the translation of exogenous and engineered DNA repair and radioprotective mechanisms, the substitution of organic molecules with fortified isoforms, and methods of slowing metabolic activity while preserving cognitive function. We conclude by presenting the known associations between radioresistance and longevity, and articulating the position that enhancing human radioresistance is likely to extend the healthspan of human spacefarers as well.

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Low-dose Photon and Simulated Solar Particle Event Proton Effects on Foxp3⁺T Regulatory Cells and other Leukocytes

Cited by 20 publications

References 52 publications

Low-Dose Total-Body γ Irradiation Modulates Immune Response to Acute Proton Radiation

Low-Dose Total-Body γ Irradiation Modulates Immune Response to Acute Proton Radiation

Ionizing Radiation Selectively Reduces Skin Regulatory T Cells and Alters Immune Function

Vive la radiorésistance!: converging research in radiobiology and biogerontology to enhance human radioresistance for deep space exploration and colonization

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Low-dose Photon and Simulated Solar Particle Event Proton Effects on Foxp3+T Regulatory Cells and other Leukocytes

Cited by 20 publications

References 52 publications

Low-Dose Total-Body γ Irradiation Modulates Immune Response to Acute Proton Radiation

Low-Dose Total-Body γ Irradiation Modulates Immune Response to Acute Proton Radiation

Ionizing Radiation Selectively Reduces Skin Regulatory T Cells and Alters Immune Function

Vive la radiorésistance!: converging research in radiobiology and biogerontology to enhance human radioresistance for deep space exploration and colonization

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Product

Resources

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Low-dose Photon and Simulated Solar Particle Event Proton Effects on Foxp3⁺T Regulatory Cells and other Leukocytes