Abstract
Whole-body irradiation impairs naïve CD4 T cell function
The Journal of immunology (1950), Vol.212(1_Supplement), pp.1215-1215_4680
05/01/2024
DOI: 10.4049/jimmunol.212.supp.1215.4680
Abstract
Abstract Advancements in nuclear power and radiotherapy have expanded new avenues for whole-body irradiation (WBI) to humans, urging the need to understand its impact on immune cells. While most studies focus on the numerical recovery of naïve T cells post-WBI, less is known regarding its impact on their function. We subjected B6 SPF mice to 0/5Gy doses of WBI and used I-Ab tetramer enrichment to track the recovery of naïve CD4s of different antigen specificities post WBI. The number of MOG40 specific CD4 T cells is diminished 10 days post-irradiation (DPR), and recovered by 40DPR. To test if they are able to induce EAE post-WBI, we administered MOG+CFA, followed by pertussis toxin (PTX). The 10DPR mice showed delayed EAE development, likely due to diminished MOG40 naïve precursors. Interestingly, the 40DPR mice potentiated EAE compared to the 0Gy mice, evidenced by increased CD4 priming in the dLN, and spine infiltration. While WBI-mediated CD4 T cell-intrinsic changes could contribute to the timing/severity of EAE, T cell-extrinsic factors could also influence disease. To test if WBI compromises the blood-brain barrier (BBB) and facilitates EAE progression, EAE is induced in +/-WBI mice without PTX. In the absence of PTX, 0Gy mice did not develop EAE, while the 10- and 40DPR mice developed EAE suggesting BBB impairment. Overall, WBI directly impacts the number and function of autoreactive CD4 T cells, while helping them enter the spine by changing the environment.
Details
- Title: Subtitle
- Whole-body irradiation impairs naïve CD4 T cell function
- Creators
- Shravan Kumar Kannan - University of IowaTi-ara Turner - University of IowaMohammad Heidarian - University of IowaShailesh Shahi - University of IowaCaleb Kim - University of MinnesotaThomas Griffith - University of Minnesota Medical CenterJohn Harty - University of IowaAshutosh Mangalam - University of IowaVladimir Badovinac - University of Iowa
- Resource Type
- Abstract
- Publication Details
- The Journal of immunology (1950), Vol.212(1_Supplement), pp.1215-1215_4680
- DOI
- 10.4049/jimmunol.212.supp.1215.4680
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Language
- English
- Date published
- 05/01/2024
- Academic Unit
- Pathology; Iowa Neuroscience Institute
- Record Identifier
- 9984747820002771
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