Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock


Long-term immunological consequences of radiation exposure in a diverse cohort of rhesus macaques.


PURPOSE: To develop an improved understanding of the delayed immunological effects of acute total body irradiation (TBI) using a diverse cohort of non-human primates as a model for an irradiated human population. METHODS: Immune recovery was evaluated in 221 rhesus macaques either left unirradiated (n=36) or previously irradiated (n=185) at 1.1 Gy 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 five 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 (sjTREC) 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 non-irradiated animals were subtle and largely restricted to younger animals and select cell populations. Subsets of monocytes, DC, T 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 five 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 naive/effector memory/central memory CD4 and CD8 T cell equilibrium and exhibited a dose-dependent increase in thymopoiesis for 2-3 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 five years of age and those receiving a high dose of radiation.

Authors: French MJ, Wuerker R, Dugan G, Olson JD, Sanders BR, Tooze JD, Caudell DL, Cline JM, Sempowski GD, Macintyre AN,
Journal: Int J Radiat Oncol Biol Phys;2022Oct23. doi:10.1016/j.ijrobp.2022.10.024
Year: 2022
PubMed: PMID: 36288757 (Go to PubMed)