Sublethal whole-body irradiation induces permanent loss and dysfunction in pathogen-specific circulating memory CD8 T...

Area of Science:

• Immunology
• Radiation Biology
• Cellular Immunology

Background:

• Nuclear energy use increases radiation exposure risks, potentially causing immune dysfunction.
• The impact of radiation on memory CD8 T cells, crucial for immunity against recurring infections and cancers, is not well understood.

Purpose of the Study:

• To investigate the long-term effects of sublethal whole-body irradiation on memory CD8 T cells.
• To assess radiation-induced numerical, differentiation, and functional impairments in memory CD8 T cells.

Main Methods:

• Utilized P14 CD8 T cell chimeric mice (P14 chimeras) infected with lymphocytic choriomeningitis virus (LCMV).
• Administered sublethal (5Gy) whole-body irradiation (WBI) and monitored P14 T cell populations and function over time.
• Assessed bacterial burden after challenging irradiated and non-irradiated mice with Listeria monocytogenes.

Main Results:

• WBI caused a rapid decline in naive and circulating memory CD8 T cells, with naive cells being more susceptible.
• Memory CD8 T cell numbers remained low for at least 9 months post-irradiation, with impaired transition to a central memory phenotype.
• Irradiated memory CD8 T cells showed functional deficits, including reduced cytokine production and impaired secondary expansion, leading to increased susceptibility to reinfection.

Conclusions:

• Sublethal radiation exposure induces long-lasting numerical and functional deficits in memory CD8 T cells.
• Impaired memory CD8 T cell differentiation and function following irradiation compromise host defense against reinfection.
• Findings underscore the immunological risks associated with radiation exposure, particularly concerning long-term immune memory.