Journal article
Whole-body irradiation causes long-term impairments in the maintenance and function of naïve CD4 T cells specific for self- and non-self-antigens
The Journal of immunology (1950), Vol.215(7), vkag174
07/10/2026
DOI: 10.1093/jimmun/vkag174
PMID: 42441427
Abstract
Whole-body irradiation (WBI) consistently induces radiation-associated lymphopenia, a complication linked to poor prognosis and reduced overall survival. Understanding the quantitative and qualitative changes in naïve CD4 T cells after WBI is critical because these cells play key roles in both host defense and the propagation of autoimmunity. Here, we show that WBI triggers a rapid decline in the naïve CD4 T-cell pool, followed by thymus-dependent numerical recovery. Shortly after WBI, mice exhibit a reduced frequency of lymphocytic choriomeningitis virus (LCMV) epitope GP66-77-specific naïve CD4 T-cell precursors. Upon infection with LCMV, this reduction leads to delayed effector expansion, impaired memory differentiation, and diminished cytokine production. WBI also disrupts blood-brain barrier (BBB) integrity, enhancing infiltration of GP66-77-specific memory CD4 T cells into the brain and promoting enrichment of brain-resident tissue-resident memory CD4 T cells. Similarly, encephalitogenic MOG38-49-specific CD4 T-cell precursors are reduced after WBI, resulting in delayed but exacerbated experimental autoimmune encephalomyelitis (EAE) compared with nonirradiated controls. WBI-mediated BBB disruption facilitates the entry of encephalitogenic MOG38-49-specific CD4 T cells into the spinal cord, promoting EAE induction and progression even in the absence of pertussis toxin administration. Together, these findings highlight both immune-intrinsic and -extrinsic effects of WBI in shaping naïve CD4 T-cell responses in the context of infection and autoimmunity.
Details
- Title: Subtitle
- Whole-body irradiation causes long-term impairments in the maintenance and function of naïve CD4 T cells specific for self- and non-self-antigens
- Creators
- Shravan Kumar Kannan - University of IowaTi-Ara J Turner - University of IowaMohammad Heidarian - University of IowaMadison R Mix - University of IowaCaleb Y Kim - University of MinnesotaCori Fain - University of IowaShailesh K Shahi - University of IowaElizabeth A Escue - University of IowaIfechukwu Ezeilo - University of IowaThomas S Griffith - University of MinnesotaAshutosh K Mangalam - University of IowaJohn T Harty - University of IowaVladimir P Badovinac - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.215(7), vkag174
- DOI
- 10.1093/jimmun/vkag174
- PMID
- 42441427
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Publisher
- OXFORD UNIV PRESS
- Grant note
- GM140881 / National Institutes of Health (NIH) T32AI007485 / NIH HHS University of Iowa Graduate College Post-Comprehensive Research Fellowship IK6BX006192 / Research Career Scientist BX00612 / Veterans Administration Merit Review Award T32GM139776 / Medical Scientist Training Program (MSTP) T32 training VA University of Iowa Distinguished Scholar R01AI114543 / National Institutes of Health (NIH) R01AI191414 / National Institutes of Health (NIH)
- Language
- English
- Date published
- 07/10/2026
- Academic Unit
- Pathology; Iowa Neuroscience Institute; Dental Research
- Record Identifier
- 9985182388902771
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