Long-Term Recovery of the Adaptive Immune System in Rhesus Macaques After Total Body Irradiation
| Autor: | Matthew J. French, Andrew N. Macintyre, Bhavna Hora, Greg Dugan, Ivo D. Shterev, J. Daniel Bourland, Tyler Evangelous, J. Mark Cline, Kristina J. Riebe, Brittany Sanders, Gregory D. Sempowski, Kevin Wiehe |
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| Rok vydání: | 2021 |
| Předmět: |
Biology Contributions
business.industry T cell R895-920 Neoplasms. Tumors. Oncology. Including cancer and carcinogens Total body irradiation Acquired immune system 030218 nuclear medicine & medical imaging Medical physics. Medical radiology. Nuclear medicine 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure Immune system Oncology Antigen 030220 oncology & carcinogenesis White blood cell Immunology medicine Cytotoxic T cell Radiology Nuclear Medicine and imaging business RC254-282 CD8 |
| Zdroj: | Advances in Radiation Oncology Advances in Radiation Oncology, Vol 6, Iss 5, Pp 100677-(2021) |
| ISSN: | 2452-1094 |
| Popis: | 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 naive 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. |
| Databáze: | OpenAIRE |
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