Dataset Information

Terminally differentiated cytotoxic CD4⁺ T cells were clonally expanded in the brain lesion of radiation-induced brain injury.

ABSTRACT:

Background

Accumulating evidence supports the involvement of adaptive immunity in the development of radiation-induced brain injury (RIBI). Our previous work has emphasized the cytotoxic function of CD8⁺ T cells in RIBI. In this study, we aimed to investigate the presence and potential roles of cytotoxic CD4⁺ T cells (CD4⁺ CTLs) in RIBI to gain a more comprehensive understanding of adaptive immunity in this context.

Main text

Utilizing single-cell RNA sequencing (scRNA-seq), we analyzed 3934 CD4⁺ T cells from the brain lesions of four RIBI patients and identified six subclusters within this population. A notable subset, the cytotoxic CD4⁺ T cells (CD4⁺ CTLs), was marked with high expression of cytotoxicity-related genes (NKG7, GZMH, GNLY, FGFBP2, and GZMB) and several chemokine and chemokine receptors (CCL5, CX3CR1, and CCL4L2). Through in-depth pseudotime analysis, which simulates the development of CD4⁺ T cells, we observed that the CD4⁺ CTLs exhibited signatures of terminal differentiation. Their functions were enriched in protein serine/threonine kinase activity, GTPase regulator activity, phosphoprotein phosphatase activity, and cysteine-type endopeptidase activity involved in the apoptotic signaling pathway. Correspondingly, mice subjected to gamma knife irradiation on the brain showed a time-dependent infiltration of CD4⁺ T cells, an increase of MHCII⁺ cells, and the existence of CD4⁺ CTLs in lesions, along with an elevation of apoptotic-related proteins. Finally, and most crucially, single-cell T-cell receptor sequencing (scTCR-seq) analysis at the patient level determined a large clonal expansion of CD4⁺ CTLs in lesion tissues of RIBI. Transcriptional factor-encoding genes TBX21, RORB, and EOMES showed positive correlations with the cytotoxic functions of CD4⁺ T cells, suggesting their potential to distinguish RIBI-related CD4⁺ CTLs from other subsets.

Conclusion

The present study enriches the understanding of the transcriptional landscape of adaptive immune cells in RIBI patients. It provides the first description of a clonally expanded CD4⁺ CTL subset in RIBI lesions, which may illuminate new mechanisms in the development of RIBI and offer potential biomarkers or therapeutic targets for the disease.

SUBMITTER: Ma X

PROVIDER: S-EPMC10948588 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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Publications

Terminally differentiated cytotoxic CD4<sup>+</sup> T cells were clonally expanded in the brain lesion of radiation-induced brain injury.

Ma Xueying X Zuo You Y Hu Xia X Chen Sitai S Zhong Ke K Xue Ruiqi R Gui Shushu S Liu Kejia K Li Shaojian S Zhu Xiaoqiu X Yang Jingwen J Deng Zhenhong Z Liu Xiaolu X Xu Yongteng Y Liu Sheng S Shi Zhongshan Z Zhou Meijuan M Tang Yamei Y

CNS neuroscience & therapeutics 20240301 3

<h4>Background</h4>Accumulating evidence supports the involvement of adaptive immunity in the development of radiation-induced brain injury (RIBI). Our previous work has emphasized the cytotoxic function of CD8<sup>+</sup> T cells in RIBI. In this study, we aimed to investigate the presence and potential roles of cytotoxic CD4<sup>+</sup> T cells (CD4<sup>+</sup> CTLs) in RIBI to gain a more comprehensive understanding of adaptive immunity in this context.<h4>Main text</h4>Utilizing single-cell ...[more]

PMID: 38499993

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Dataset Information

Terminally differentiated cytotoxic CD4⁺ T cells were clonally expanded in the brain lesion of radiation-induced brain injury.

Background

Main text

Conclusion

Publications

Terminally differentiated cytotoxic CD4<sup>+</sup> T cells were clonally expanded in the brain lesion of radiation-induced brain injury.

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OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Terminally differentiated cytotoxic CD4+ T cells were clonally expanded in the brain lesion of radiation-induced brain injury.

Background

Main text

Conclusion

Publications

Terminally differentiated cytotoxic CD4<sup>+</sup> T cells were clonally expanded in the brain lesion of radiation-induced brain injury.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Terminally differentiated cytotoxic CD4⁺ T cells were clonally expanded in the brain lesion of radiation-induced brain injury.