Medical radiation exposure has doubled over the past decade, largely due to diagnostic tools such as X-rays and CT scans. While often lifesaving, radiation weakens the immune system by depleting lymphocytes, leaving individuals more vulnerable to infections and cancer. A new study explores how different subsets of memory CD8 T cells respond to radiation and what this means for immune recovery (Figure 1).
Figure 1: Generation of 1M and 4M CD8 T cell populations within the same host. (A) Experimental design. Naïve Thy1.1/1.1 and tertiary memory (3M) Thy1.1/1.2 TCR-Tg P14 CD8 T cells were co-adoptively transferred into naïve Thy1.2/1.2 C57BL/6 (B6) hosts at a ratio of 1:10, followed by LCMV-Arm (2 × 105 PFU intraperitoneally) infection to generate allelically distinct primary memory (1M) and quaternary memory (4M) populations. (B) Representative gating of TCR-Tg P14 and endogenous Thy1.2/1.2 CD8 T cells (left) and of 1M and 4M P14 CD8 T cells (right). (C) Expression of CD62L, CD127, CD122, KLRG1, and CX3CR1 on gated 1M and 4M P14 CD8 T cells. Representative histograms are shown. (D) Quantification of geometric mean fluorescence intensity (gMFI) of cell surface markers from panel C. Data are representative from at least 3 independent experiments with at least 5 mice per group. Error bars represent the SD of the mean. ***P < 0.001 using 2-tailed Student’s t test.
CD8 T cells under stress
CD8 T cells are critical for eliminating pathogens and cancer cells. Their memory subtypes depend on prior antigen exposure:
- 1M CD8 T cells arise after a single infection or vaccination.
- 4M CD8 T cells develop after multiple exposures or booster vaccinations.
Previous work showed that 1M cells are more resistant to radiation-induced death than naïve CD8 T cells, but their numbers fail to recover. Elizabeth Escue, MS, and colleagues investigated whether 4M CD8 T cells fared differently.
Findings
- Both 1M and 4M CD8 T cells were susceptible to radiation-induced cell death.
- 1M CD8 T cells stabilized after the acute damage phase.
- 4M CD8 T cells continued to decline over time, showing greater long-term impairment.
- All irradiated memory subsets showed reduced cytokine production, but 4M CD8 T cells were especially poor at proliferating after new antigen exposure.
The study highlights that restoring immune memory in radiation-exposed individuals requires addressing multiple layers of CD8 T cell dysfunction.
Journal article: Escue, E.A., et al. 2025. The ability of memory CD8 T cell subsets to numerically and functionally recover following whole body irradiation is influenced by their history of cognate antigen exposures, The Journal of Immunology.
Summary by Stefan Botha
