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Long-Term Immunological Consequences of Radiation Exposure in a Diverse Cohort of Rhesus Macaques.

Publication ,  Journal Article
French, MJ; Wuerker, R; Dugan, G; Olson, JD; Sanders, BR; Tooze, JA; Caudell, DL; Cline, JM; Sempowski, GD; Macintyre, AN
Published in: Int J Radiat Oncol Biol Phys
March 15, 2023

PURPOSE: The aim of this study was to develop an improved understanding of the delayed immunologic effects of acute total body irradiation (TBI) using a diverse cohort of nonhuman primates as a model for an irradiated human population. METHODS AND MATERIALS: Immune recovery was evaluated in 221 rhesus macaques either left unirradiated (n = 36) or previously irradiated (n = 185) at 1.1 to 8.5 Gy TBI (median, 6.5 Gy) when aged 2.1 to 15.5 years (median, 4.2 years). Blood was drawn annually for up to 5 years total between 0.5 and 14.3 years after exposure. Blood was analyzed by complete blood count, immunophenotyping of monocytes, dendritic cells (DC) and lymphocytes by flow cytometry, and signal joint T-cell receptor exclusion circle quantification in isolated peripheral blood CD4 and CD8 T cells. Animals were categorized by age, irradiation status, and time since irradiation. Sex-adjusted means of immune metrics were evaluated by generalized estimating equation models to identify cell populations altered by TBI. RESULTS: Overall, the differences between irradiated and nonirradiated animals were subtle and largely restricted to younger animals and select cell populations. Subsets of monocytes, DC, T cells, and B cells showed significant interaction effects between radiation dose and age after adjustment for sex. Irradiation at a young age caused transient increases in the percentage of peripheral blood myeloid DC and dose-dependent changes in monocyte balance for at least 5 years after TBI. TBI also led to a sustained decrease in the percentage of circulating memory B cells. Young irradiated animals exhibited statistically significant and prolonged disruption of the naïve/effector memory/central memory CD4 and CD8 T-cell equilibrium and exhibited a dose-dependent increase in thymopoiesis for 2 to 3 years after exposure. CONCLUSIONS: This study indicates TBI subtly but significantly alters the circulating proportions of cellular mediators of adaptive immune memory for several years after irradiation, especially in macaques under 5 years of age and those receiving a high dose of radiation.

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Published In

Int J Radiat Oncol Biol Phys

DOI

EISSN

1879-355X

Publication Date

March 15, 2023

Volume

115

Issue

4

Start / End Page

945 / 956

Location

United States

Related Subject Headings

  • Radiation Exposure
  • Oncology & Carcinogenesis
  • Monocytes
  • Macaca mulatta
  • Lymphocytes
  • Humans
  • Child, Preschool
  • CD8-Positive T-Lymphocytes
  • Animals
  • 5105 Medical and biological physics
 

Citation

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French, M. J., Wuerker, R., Dugan, G., Olson, J. D., Sanders, B. R., Tooze, J. A., … Macintyre, A. N. (2023). Long-Term Immunological Consequences of Radiation Exposure in a Diverse Cohort of Rhesus Macaques. Int J Radiat Oncol Biol Phys, 115(4), 945–956. https://doi.org/10.1016/j.ijrobp.2022.10.024
French, Matthew J., Ryan Wuerker, Greg Dugan, John D. Olson, Brittany R. Sanders, Janet A. Tooze, David L. Caudell, J Mark Cline, Gregory D. Sempowski, and Andrew N. Macintyre. “Long-Term Immunological Consequences of Radiation Exposure in a Diverse Cohort of Rhesus Macaques.Int J Radiat Oncol Biol Phys 115, no. 4 (March 15, 2023): 945–56. https://doi.org/10.1016/j.ijrobp.2022.10.024.
French MJ, Wuerker R, Dugan G, Olson JD, Sanders BR, Tooze JA, et al. Long-Term Immunological Consequences of Radiation Exposure in a Diverse Cohort of Rhesus Macaques. Int J Radiat Oncol Biol Phys. 2023 Mar 15;115(4):945–56.
French, Matthew J., et al. “Long-Term Immunological Consequences of Radiation Exposure in a Diverse Cohort of Rhesus Macaques.Int J Radiat Oncol Biol Phys, vol. 115, no. 4, Mar. 2023, pp. 945–56. Pubmed, doi:10.1016/j.ijrobp.2022.10.024.
French MJ, Wuerker R, Dugan G, Olson JD, Sanders BR, Tooze JA, Caudell DL, Cline JM, Sempowski GD, Macintyre AN. Long-Term Immunological Consequences of Radiation Exposure in a Diverse Cohort of Rhesus Macaques. Int J Radiat Oncol Biol Phys. 2023 Mar 15;115(4):945–956.
Journal cover image

Published In

Int J Radiat Oncol Biol Phys

DOI

EISSN

1879-355X

Publication Date

March 15, 2023

Volume

115

Issue

4

Start / End Page

945 / 956

Location

United States

Related Subject Headings

  • Radiation Exposure
  • Oncology & Carcinogenesis
  • Monocytes
  • Macaca mulatta
  • Lymphocytes
  • Humans
  • Child, Preschool
  • CD8-Positive T-Lymphocytes
  • Animals
  • 5105 Medical and biological physics