Delineating the short- and long-term impact of ionizing radiation on antigen-inexperienced CD8+ T cell subsets

Mohammad Heidarian; Shravan K Kannan; Whitney Swanson; Thomas S Griffith; John T Harty; Vladimir P Badovinac

doi:10.1172/jci.insight.194201

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Delineating the short- and long-term impact of ionizing radiation on antigen-inexperienced CD8+ T cell subsets

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Delineating the short- and long-term impact of ionizing radiation on antigen-inexperienced CD8+ T cell subsets

Mohammad Heidarian, Shravan K Kannan, Whitney Swanson, Thomas S Griffith, John T Harty and Vladimir P Badovinac

JCI insight, Vol.10(20), e194201

09/23/2025

DOI: 10.1172/jci.insight.194201

PMCID: PMC12487864

PMID: 40762983

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Abstract

Radiation-induced lymphopenia (RIL) remains a challenging side effect of radiation therapy, often associated with poor prognosis and reduced overall survival. Although CD8+ T cells are highly radiosensitive, the dynamics of quantitative and qualitative changes to the CD8 T cell pool following exposure to high doses of ionizing radiation (IR) remains understudied. Herein, we sought to determine the long-term impact of sublethal whole body irradiation (WBI) on antigen (Ag)-inexperienced CD8 T cell pool, comprised of naïve (TN) and virtual memory (TVM) CD8+ T cells. We show that although both TN and TVM cells gradually regenerate after WBI-induced loss, TN recovery only occurs through de novo thymic production. Despite the numerical restoration, the subset and phenotypic composition of post-recovery Ag-inexperienced CD8+ T cells do not qualitatively recapitulate the pre-WBI state. Specifically, the frequency of TVM cells is increased, especially during the early stages of recovery. Within the TN subset, a lasting overrepresentation of Ly6C+CD122+ cells and an altered TCR clonotype diversity are also observed. Overall, our data highlight the dynamic changes to the Ag-inexperienced CD8+ T cell pool upon recovery from RIL.

Inflammation

Immunology

Radiation therapy

T cells

Details

Title: Subtitle: Delineating the short- and long-term impact of ionizing radiation on antigen-inexperienced CD8+ T cell subsets
Creators: Mohammad Heidarian - University of Iowa
Shravan K Kannan - University of Iowa
Whitney Swanson - University of Minnesota
Thomas S Griffith - University of Minnesota
John T Harty - University of Iowa
Vladimir P Badovinac - University of Iowa
Resource Type: Journal article
Publication Details: JCI insight, Vol.10(20), e194201
DOI: 10.1172/jci.insight.194201
PMID: 40762983
PMCID: PMC12487864
NLM abbreviation: JCI Insight
ISSN: 2379-3708
eISSN: 2379-3708
Publisher: AMER SOC CLINICAL INVESTIGATION INC
Grant note: National Institutes of Health (NIH): R01AI114543, R01AI042767, GM140881 Veterans Administration Merit Review Award: BX001324 Department of Veterans Affairs: IK6BX006192
This study was supported by National Institutes of Health (NIH) grants R01AI114543 (to VPB and JTH), R01AI042767 (to JTH), and GM140881 (to TSG) and a Veterans Administration Merit Review Award (BX001324 to TSG). TSG is the recipient of a Research Career Scientist award (IK6BX006192) from the Department of Veterans Affairs. VPB is a University of Iowa Distinguished Scholar. We thank members of the Harty and Badovinac labs for valuable discussions. We also thank Vahid Nasirian at Ionizing Radiation Services at Free Radical Research Core for assisting with WBI of mice. This work is the result of NIH funding, in whole or in part, and is subject to the NIH Public Access Policy. Through acceptance of this federal funding, the NIH has been given a right to make the work publicly available in PubMed Central.
Language: English
Electronic publication date: 08/05/2025
Date published: 09/23/2025
Academic Unit: Pathology
Record Identifier: 9984945089902771

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