Relative alterations in blood mononuclear cell populations reflect radiation injury in mice

Chambers, Kelley A.; Harrington, Noel P.; Ross, W. M.; Filion, Lionel G.

doi:10.1002/(sici)1097-0320(19980101)31:1<45::aid-cyto6>3.0.co;2-i

Cited by 34 publications

(13 citation statements)

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“…NK cells have been reported to be relatively resistant to radiation (26). To examine this, the percentage of NK cells in wild-type B6 mice was analyzed before and 6 h after irradiation, the time point when the HSC were transplanted in our model.…”

Section: Nk Cells Are the Major Effector Cell In The Rejection Of Pursupporting

confidence: 92%

NK Cells Play a Critical Role in the Regulation of Class I-Deficient Hemopoietic Stem Cell Engraftment: Evidence for NK Tolerance Correlates with Receptor Editing

Huang

Rezzoug

et al. 2005

The Journal of Immunology

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The role that NK cells play in the rejection of hemopoietic stem cell (HSC) and tolerance induction has remained controversial. In this study, we examined whether NK cells play a direct role in the rejection of HSC. Purified HSC from MHC class II-deficient mice engrafted readily in congenic mice, while HSC from class I-deficient donors (β2-microglobulin−/− (β2m−/−)) failed to engraft. Recipient mice lacking CD8+, CD4+, or T cells also rejected HSC from class I-deficient donors, pointing directly to NK cells as the effector in rejection of HSC. Recipients, deficient in or depleted of NK cells, engrafted readily with β2m−/− HSC. Expression of the activating Ly-49D and inhibitory Ly-49G2 receptors on recipient NK cells was significantly decreased in these β2m−/−→B6 chimeras, and the proportion of donor NK cells expressing Ly-49D was also significantly decreased. Notably, β2m−/− chimeras accepted β2m−/− HSC in second transplants, demonstrating that NK cells in the chimeras had been tolerized to β2m−/−. Taken together, our data demonstrate that NK cells play a direct role in the regulation of HSC engraftment, and down-regulation and/or deletion of specific NK subsets in mixed chimeras can contribute to the induction of NK cell tolerance in vivo. Moreover, our data show that bone marrow-derived elements significantly contribute to NK cell development and tolerance.

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Section: Nk Cells Are the Major Effector Cell In The Rejection Of Pursupporting

confidence: 92%

NK Cells Play a Critical Role in the Regulation of Class I-Deficient Hemopoietic Stem Cell Engraftment: Evidence for NK Tolerance Correlates with Receptor Editing

Huang

Rezzoug

et al. 2005

The Journal of Immunology

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“…Our observations are in agreement with multiple rodent studies that describe B cells to be more radiosensitive than T cells [77][78][79][80]. Our studies expand upon these previous studies and show that, within the B cell population in RMs, the frequency of naive and switched memory B cells were the most responsive to ionizing radiation, while the MZlike memory subset remained somewhat resistant to change.…”

Section: Discussionmentioning

confidence: 99%

Impact of irradiation and immunosuppressive agents on immune system homeostasis in rhesus macaques

Meyer

Walker

Dewane

et al. 2015

Clinical and Experimental Immunology

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SummaryIn this study we examined the effects of non-myeloablative total body irradiation (TBI) in combination with immunosuppressive chemotherapy on immune homeostasis in rhesus macaques. Our results show that the administration of cyclosporin A or tacrolimus without radiotherapy did not result in lymphopenia. The addition of TBI to the regimen resulted in lymphopenia as well as alterations in the memory/naive ratio following reconstitution of lymphocyte populations. Dendritic cell (DC) numbers in whole blood were largely unaffected, while the monocyte population was altered by immunosuppressive treatment. Irradiation also resulted in increased levels of circulating cytokines and chemokines that correlated with T cell proliferative bursts and with the shift towards memory T cells. We also report that anti-thymocyte globulin (ATG) treatment and CD3 immunotoxin administration resulted in a selective and rapid depletion of naive CD4 and CD8 T cells and increased frequency of memory T cells. We also examined the impact of these treatments on reactivation of latent simian varicella virus (SVV) infection as a model of varicella zoster virus (VZV) infection of humans. None of the treatments resulted in overt SVV reactivation; however, select animals had transient increases in SVV-specific T cell responses following immunosuppression, suggestive of subclinical reactivation. Overall, we provide detailed observations into immune modulation by TBI and chemotherapeutic agents in rhesus macaques, an important research model of human disease.

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“…This acute radiation hematopoietic syndrome is primarily attributed to apoptosis induction of HPCs, and the BM injury is mainly ascribed to persistent HSC damage. While the effects of gamma irradiation on the hematopoietic system have been extensively documented, much less is known about the effects of proton irradiation (10, 11). Several recent studies have reported proton radiation-induced acute effects on the mouse hematopoietic system (12–17).…”

Section: Introductionmentioning

confidence: 99%

Whole-Body Proton Irradiation Causes Long-Term Damage to Hematopoietic Stem Cells in Mice

Chang¹,

Wei²,

Wang³

et al. 2015

Radiation Research

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Space flight poses certain health risks to astronauts, including exposure to space radiation, with protons accounting for more than 80% of deep-space radiation. Proton radiation is also now being used with increasing frequency in the clinical setting to treat cancer. For these reasons, there is an urgent need to better understand the biological effects of proton radiation on the body. Such improved understanding could also lead to more accurate assessment of the potential health risks of proton radiation, as well as the development of improved strategies to prevent and mitigate its adverse effects. Previous studies have shown that exposure to low doses of protons is detrimental to mature leukocyte populations in peripheral blood, however, the underlying mechanisms are not known. Some of these detriments may be attributable to damage to hematopoietic stem cells (HSCs) that have the ability to self-renew, proliferate and differentiate into different lineages of blood cells through hematopoietic progenitor cells (HPCs). The goal of this study was to investigate the long-term effects of low-dose proton irradiation on HSCs. We exposed C57BL/6J mice to 1.0 Gy whole-body proton irradiation (150 MeV) and then studied the effects of proton radiation on HSCs and HPCs in the bone marrow (BM) 22 weeks after the exposure. The results showed that mice exposed to 1.0 Gy whole-body proton irradiation had a significant and persistent reduction of BM HSCs compared to unirradiated controls. In contrast, no significant changes were observed in BM HPCs after proton irradiation. Furthermore, irradiated HSCs and their progeny exhibited a significant impairment in clonogenic function, as revealed by the cobblestone area-forming cell (CAFC) and colony-forming cell assays, respectively. These long-term effects of proton irradiation on HSCs may be attributable to the induction of chronic oxidative stress in HSCs, because HSCs from irradiated mice exhibited a significant increase in NADPH oxidase 4 (NOX4) mRNA expression and reactive oxygen species (ROS) production. In addition, the increased production of ROS in HSCs was associated with a significant reduction in HSC quiescence and an increase in DNA damage. These findings indicate that exposure to proton radiation can lead to long-term HSC injury, probably in part by radiation-induced oxidative stress.

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Relative alterations in blood mononuclear cell populations reflect radiation injury in mice

Cited by 34 publications

References 0 publications

NK Cells Play a Critical Role in the Regulation of Class I-Deficient Hemopoietic Stem Cell Engraftment: Evidence for NK Tolerance Correlates with Receptor Editing

NK Cells Play a Critical Role in the Regulation of Class I-Deficient Hemopoietic Stem Cell Engraftment: Evidence for NK Tolerance Correlates with Receptor Editing

Impact of irradiation and immunosuppressive agents on immune system homeostasis in rhesus macaques

Whole-Body Proton Irradiation Causes Long-Term Damage to Hematopoietic Stem Cells in Mice

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