Advertisement

ResearchIn-Press PreviewImmunologyNeuroscienceVascular biology Open Access | 10.1172/JCI203868

CD8⁺ Regulatory T Cells Shorten Neutrophil Lifespan to Reduce Hemorrhagic Transformation After Ischemic Stroke

Jianan Lu,1 Qia Zhang,1 Jiarui Chen,1 Huaming Li,1 An Ping,1 Ziyang Jin,1 Xiaotao Zhang,1 Yichen Gu,1 Xuejiao Dai,2 Zihong Chen,1 Yajun Qian,1 Guoqiang Zhang,1 Jun Yu,1 Jianmin Zhang,1 and Ligen Shi1

1Department of Neurosurgery, Zhejiang University, Hangzhou, China

2Department of Health Management Center, Zhejiang University, Hangzhou, China

Find articles by Lu, J. in: PubMed | Google Scholar

1Department of Neurosurgery, Zhejiang University, Hangzhou, China

2Department of Health Management Center, Zhejiang University, Hangzhou, China

Find articles by Zhang, Q. in: PubMed | Google Scholar

1Department of Neurosurgery, Zhejiang University, Hangzhou, China

2Department of Health Management Center, Zhejiang University, Hangzhou, China

Find articles by Chen, J. in: PubMed | Google Scholar

1Department of Neurosurgery, Zhejiang University, Hangzhou, China

2Department of Health Management Center, Zhejiang University, Hangzhou, China

Find articles by Li, H. in: PubMed | Google Scholar

1Department of Neurosurgery, Zhejiang University, Hangzhou, China

2Department of Health Management Center, Zhejiang University, Hangzhou, China

Find articles by Ping, A. in: PubMed | Google Scholar

1Department of Neurosurgery, Zhejiang University, Hangzhou, China

2Department of Health Management Center, Zhejiang University, Hangzhou, China

Find articles by Jin, Z. in: PubMed | Google Scholar

1Department of Neurosurgery, Zhejiang University, Hangzhou, China

2Department of Health Management Center, Zhejiang University, Hangzhou, China

Find articles by Zhang, X. in: PubMed | Google Scholar

1Department of Neurosurgery, Zhejiang University, Hangzhou, China

2Department of Health Management Center, Zhejiang University, Hangzhou, China

Find articles by Gu, Y. in: PubMed | Google Scholar

1Department of Neurosurgery, Zhejiang University, Hangzhou, China

2Department of Health Management Center, Zhejiang University, Hangzhou, China

Find articles by Dai, X. in: PubMed | Google Scholar

1Department of Neurosurgery, Zhejiang University, Hangzhou, China

2Department of Health Management Center, Zhejiang University, Hangzhou, China

Find articles by Chen, Z. in: PubMed | Google Scholar

1Department of Neurosurgery, Zhejiang University, Hangzhou, China

2Department of Health Management Center, Zhejiang University, Hangzhou, China

Find articles by Qian, Y. in: PubMed | Google Scholar

1Department of Neurosurgery, Zhejiang University, Hangzhou, China

2Department of Health Management Center, Zhejiang University, Hangzhou, China

Find articles by Zhang, G. in: PubMed | Google Scholar

1Department of Neurosurgery, Zhejiang University, Hangzhou, China

2Department of Health Management Center, Zhejiang University, Hangzhou, China

Find articles by Yu, J. in: PubMed | Google Scholar

1Department of Neurosurgery, Zhejiang University, Hangzhou, China

2Department of Health Management Center, Zhejiang University, Hangzhou, China

Find articles by Zhang, J. in: PubMed | Google Scholar

1Department of Neurosurgery, Zhejiang University, Hangzhou, China

2Department of Health Management Center, Zhejiang University, Hangzhou, China

Find articles by Shi, L. in: PubMed | Google Scholar |

Published September 1, 2026 - More info

J Clin Invest. https://doi.org/10.1172/JCI203868.
Copyright © 2026, Lu et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published September 1, 2026 - Version history
View PDF
Abstract

The neutrophil-to-lymphocyte ratio (NLR) is associated with unfavorable prognosis and hemorrhagic transformation (HT) in patients with ischemic stroke, yet the underlying mechanisms remain unclear. Using patient samples and a murine stroke model, we identified CD8⁺ regulatory T cells (CD8 Tregs) key regulators of neutrophil homeostasis after ischemic stroke, thereby limiting endothelial disruption and HT. Loss of CD8 Tregs expanded circulating neutrophils by extending their lifespan rather than altering proliferation, bone marrow release, or direct cytotoxicity. Mechanistically, CD8 Tregs shortened neutrophil lifespan by modulating HIF-1α–dependent glycolytic activity and relieving PD-L1–mediated suppression of bone marrow clearance. Finally, co-culture experiments with human CD8 Tregs and neutrophils revealed similar neutrophil-regulatory effects, accompanied by improved endothelial barrier integrity. These findings reveal a previously unrecognized CD8 Treg–neutrophil axis and suggest potential therapeutic strategies for preventing HT after stroke.

Graphical Abstract
graphical abstract
Supplemental material

View

Version history
  • Version 1 (September 1, 2026): In-Press Preview
Advertisement
Advertisement