Journal article
Sublethal whole-body irradiation induces permanent loss and dysfunction in pathogen-specific circulating memory CD8 T cell populations
Proceedings of the National Academy of Sciences - PNAS, Vol.120(27), e2302785120
07/04/2023
DOI: 10.1073/pnas.2302785120
PMCID: PMC10318958
PMID: 37364124
Abstract
The increasing use of nuclear energy sources inevitably raises the risk of accidental or deliberate radiation exposure and associated immune dysfunction. However, the extent to which radiation exposure impacts memory CD8 T cells, potent mediators of immunity to recurring intracellular infections and malignancies, remains understudied. Using P14 CD8 T cell chimeric mice (P14 chimeras) with an lymphocytic choriomeningitis virus (LCMV) infection model, we observed that sublethal (5Gy) whole-body irradiation (WBI) induced a rapid decline in the number of naive (T
) and P14 circulating memory CD8 T cells (T
), with the former being more susceptible to radiation-induced numeric loss. While T
cell numbers rapidly recovered, as previously described, the number of P14 T
cells remained low at least 9 mo after radiation exposure. Additionally, the remaining P14 T
in irradiated hosts exhibited an inefficient transition to a central memory (CD62L
) phenotype compared to nonirradiated P14 chimeras. WBI also resulted in long-lasting T cell intrinsic deficits in memory CD8 T cells, including diminished cytokine and chemokine production along with impaired secondary expansion upon cognate Ag reencounter. Irradiated P14 chimeras displayed significantly higher bacterial burden after challenge with
expressing the LCMV GP
epitope relative to nonirradiated controls, likely due to radiation-induced numerical and functional impairments. Taken together, our findings suggest that sublethal radiation exposure caused a long-term numerical, impaired differentiation, and functional dysregulation in preexisting T
, rendering previously protected hosts susceptible to reinfection.
Details
- Title: Subtitle
- Sublethal whole-body irradiation induces permanent loss and dysfunction in pathogen-specific circulating memory CD8 T cell populations
- Creators
- Mohammad Heidarian - University of IowaIsaac J Jensen - University of IowaShravan Kumar Kannan - University of IowaLecia L Pewe - University of IowaMariah Hassert - University of IowaSungRye Park - Center for DiscoveryHai-Hui Xue - Hackensack University Medical CenterJohn T Harty - University of IowaVladimir P Badovinac - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.120(27), e2302785120
- DOI
- 10.1073/pnas.2302785120
- PMID
- 37364124
- PMCID
- PMC10318958
- eISSN
- 1091-6490
- Grant note
- F32AI174382 / NIAID NIH HHS
- Language
- English
- Date published
- 07/04/2023
- Academic Unit
- Pathology
- Record Identifier
- 9984438859602771
Metrics
9 Record Views