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Long-Term Recovery of the Adaptive Immune System in Rhesus Macaques After Total Body Irradiation.
Macintyre, Andrew N; French, Matthew J; Sanders, Brittany R; Riebe, Kristina J; Shterev, Ivo D; Wiehe, Kevin; Hora, Bhavna; Evangelous, Tyler; Dugan, Greg; Bourland, J Daniel; Cline, J Mark; Sempowski, Gregory D.
Afiliação
  • Macintyre AN; Duke Human Vaccine Institute and Department of Medicine, Duke University School of Medicine, Durham, North Carolina.
  • French MJ; Duke Human Vaccine Institute and Department of Medicine, Duke University School of Medicine, Durham, North Carolina.
  • Sanders BR; Duke Human Vaccine Institute and Department of Medicine, Duke University School of Medicine, Durham, North Carolina.
  • Riebe KJ; Duke Human Vaccine Institute and Department of Medicine, Duke University School of Medicine, Durham, North Carolina.
  • Shterev ID; Duke Human Vaccine Institute and Department of Medicine, Duke University School of Medicine, Durham, North Carolina.
  • Wiehe K; Duke Human Vaccine Institute and Department of Medicine, Duke University School of Medicine, Durham, North Carolina.
  • Hora B; Duke Human Vaccine Institute and Department of Medicine, Duke University School of Medicine, Durham, North Carolina.
  • Evangelous T; Duke Human Vaccine Institute and Department of Medicine, Duke University School of Medicine, Durham, North Carolina.
  • Dugan G; Department of Pathology/Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
  • Bourland JD; Department of Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
  • Cline JM; Department of Pathology/Comparative Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
  • Sempowski GD; Duke Human Vaccine Institute and Department of Medicine, Duke University School of Medicine, Durham, North Carolina.
Adv Radiat Oncol ; 6(5): 100677, 2021.
Article em En | MEDLINE | ID: mdl-34646962
ABSTRACT

PURPOSE:

Ionizing radiation causes acute damage to hematopoietic and immune cells, but the long-term immunologic consequences of irradiation are poorly understood. We therefore performed a prospective study of the delayed immune effects of radiation using a rhesus macaque model. METHODS AND MATERIALS Ten macaques received 4 Gy high-energy x-ray total body irradiation (TBI) and 6 control animals received sham irradiation. TBI caused transient lymphopenia that resolved over several weeks. Once white blood cell counts recovered, flow cytometry was used to immunophenotype the circulating adaptive immune cell populations 4, 9, and 21 months after TBI. Data were fit using a mixed-effects model to determine age-dependent, radiation-dependent, and interacting effects. T cell receptor (TCR) sequencing and quantification of TCR Excision Circles were used to determine relative contributions of thymopoiesis and peripheral expansion to T cell repopulation. Two years after TBI, the cohort was vaccinated with a 23-valent pneumococcal polysaccharide vaccine and a tetravalent influenza hemagglutinin vaccine.

RESULTS:

Aging, but not TBI, led to significant changes in the frequencies of dendritic cells, CD4 and CD8 T cells, and B cells. However, irradiated animals exhibited increased frequencies of central memory T cells and decreased frequencies of naïve T cells. These consequences of irradiation were time-dependent and more prolonged in the CD8 T cell population. Irradiation led to transient increases in CD8+ T cell TCR Excision Circles and had no significant effect on TCR sequence entropy, indicating T cell recovery was partially mediated by thymopoiesis. Animals that were irradiated and then vaccinated showed normal immunoglobulin G binding and influenza neutralization titers in response to the 4 protein antigens but weaker immunoglobulin G binding titers to 10 of the 23 polysaccharide antigens.

CONCLUSIONS:

These findings indicate that TBI causes subtle but long-lasting immune defects that are evident years after recovery from lymphopenia.

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Observational_studies / Prognostic_studies Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Observational_studies / Prognostic_studies Idioma: En Ano de publicação: 2021 Tipo de documento: Article