Whole-body irradiation causes long-term impairments in the maintenance and function of naïve CD4 T cells specific for self- and non-self-antigens.
SK, K., TJ, T., M, H., MR, M., CY, K., C, F., SK, S., EA, E., I, E., & TS, G. (2026). Whole-body irradiation causes long-term impairments in the maintenance and function of naïve CD4 T cells specific for self- and non-self-antigens.. Journal of immunology (Baltimore, Md. : 1950). https://doi.org/10.1093/jimmun/vkag174
SK K, TJ T, M H, MR M, CY K, C F, et al. Whole-body irradiation causes long-term impairments in the maintenance and function of naïve CD4 T cells specific for self- and non-self-antigens.. Journal of immunology (Baltimore, Md. : 1950). 2026; doi: 10.1093/jimmun/vkag174
SK K, TJ T, M H, et al. Whole-body irradiation causes long-term impairments in the maintenance and function of naïve CD4 T cells specific for self- and non-self-antigens.[J]. Journal of immunology (Baltimore, Md. : 1950). 2026. DOI: 10.1093/jimmun/vkag174.
@article{sk2026,
author = {Kannan SK and Turner TJ and Heidarian M and Mix MR and Kim CY and Fain C and Shahi SK and Escue EA and Ezeilo I and Griffith TS},
title = {Whole-body irradiation causes long-term impairments in the maintenance and function of naïve CD4 T cells specific for self- and non-self-antigens.},
journal = {Journal of immunology (Baltimore, Md. : 1950)},
year = {2026},
doi = {10.1093/jimmun/vkag174},
note = {PMID: 42441427},
}
TY - JOUR AU - Kannan SK AU - Turner TJ AU - Heidarian M AU - Mix MR AU - Kim CY AU - Fain C AU - Shahi SK AU - Escue EA AU - Ezeilo I AU - Griffith TS TI - Whole-body irradiation causes long-term impairments in the maintenance and function of naïve CD4 T cells specific for self- and non-self-antigens. T2 - Journal of immunology (Baltimore, Md. : 1950) PY - 2026 DO - 10.1093/jimmun/vkag174 AN - PMID:42441427 ER -
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.