Whole-Thorax Irradiation Induces Persistent T Cell Clonal Dysregulation in Pediatric Rhesus Macaques.

Area of Science:

• Immunology
• Radiation Biology
• Pediatric Health

Background:

• The thymus is crucial for T cell development and immune response.
• Ionizing radiation exposure can severely damage the thymus and T cells, leading to lymphopenia and increased infection risk.
• Current countermeasures for radiation-induced thymic injury are lacking, necessitating effective preclinical models.

Purpose of the Study:

• To characterize the effects of whole-thorax irradiation on the thymus of pediatric non-human primates (NHPs).
• To evaluate the NHP model for studying radiation-induced thymic injury in children.
• To identify potential targets for medical countermeasures against radiation effects on the thymus.

Main Methods:

• Pediatric rhesus macaque NHPs received 10 Gy whole-thorax irradiation.
• Computed tomography (CT) was used for in vivo assessment of thymic density and volume.
• Histopathological staining and molecular analyses were performed to evaluate thymic architecture, T cell receptor diversity, and thymic output.

Main Results:

• CT assessments did not correlate with thymic weight changes 19 weeks post-irradiation.
• Histopathology revealed disrupted thymic architecture four months after irradiation in some animals.
• Molecular analysis indicated decreased thymic output, reduced T cell receptor diversity, and clonal expansion.

Conclusions:

• The pediatric NHP whole-thorax irradiation model is suitable for studying radiation-induced thymic injury.
• This model can aid in developing medical countermeasures for children exposed to radiation.
• Radiation significantly impacts thymic function and T cell receptor repertoire, highlighting the need for protective strategies.