Cited by 722Neuroinflammation and Neurodegeneration MechanismsAcute Ischemic Stroke ManagementNeurological Disease Mechanisms and Treatments

Role of T Lymphocytes and Interferon-γ in Ischemic Stroke

Yilmaz, Gokhan, Arumugam, Thiruma V., Stokes, Karen Y., Granger, D. Neil·2006·Circulation

Abstract

BACKGROUND: Although lymphocyte recruitment and activation are associated with cerebral ischemia-reperfusion (I/R) injury, the contributions of specific lymphocyte subpopulations and lymphocyte-derived interferon-gamma (IFN-gamma) to stroke remain unknown. The objectives of this study were to define the contribution of specific populations of lymphocytes to the inflammatory and prothrombogenic responses elicited in the cerebral microvasculature by I/R and to investigate the role of T-cell-associated IFN-gamma in the pathogenesis of ischemic stroke. METHODS AND RESULTS: Middle cerebral artery occlusion was induced for 1 hour (followed by 4 or 24 hours of reperfusion) in wild-type mice and mice deficient in lymphocytes (Rag1(-/-)), CD4+ T cells, CD8+ T cells, B cells, or IFN-gamma. Platelet and leukocyte adhesion was assessed in cortical venules with intravital video microscopy. Neurological deficit and infarct volume were determined 24 hours after reperfusion. Rag1(-/-), CD4+ T-cell(-/-), CD8+ T-cell(-/-), and IFN-gamma(-/-) mice exhibited comparable significant reductions in I/R-induced leukocyte and platelet adhesion compared with wild-type mice exposed to I/R. Infarct volume was reduced and I/R-induced neurological deficit was improved in immunodeficient Rag1(-/-) mice. These protective responses were reversed in Rag1(-/-) mice reconstituted with either wild-type or, to a lesser extent, IFN-gamma(-/-) splenocytes. B-cell-deficient mice failed to show improvement against ischemic stroke injury. CONCLUSIONS: These findings indicate that CD4+ and CD8+ T lymphocytes, but not B lymphocytes, contribute to the inflammatory and thrombogenic responses, brain injury, and neurological deficit associated with experimental stroke. Although IFN-gamma plays a pivotal role in stroke-induced inflammatory responses, T lymphocytes appear to be a minor source of this cytokine.

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Crossref · 10.1161/circulationaha.105.593046

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Authors
Yilmaz, G., Arumugam, T. V., Stokes, K. Y., & Granger, D. N.
Affiliations
  • From the Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport.
  • Louisiana State University Health Sciences Center Shreveport (US)
Venue
Circulation
Published
2006-05-02
Volume
113
Issue
17
Pages
2105-2112
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
OpenAlex
W2097756768
Cited by
722
References
33
Citations by year
2026: 24 · 2025: 41 · 2024: 32 · 2023: 29 · 2022: 46 · 2021: 49 · 2020: 37 · 2019: 39 · 2018: 44 · 2017: 36 · 2016: 50 · 2015: 39 · 2014: 51 · 2013: 46 · 2012: 33
FWCI
14.04
Type
journal article
Language
en
Open access
closed
Locations
  • Circulation (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Heart, Lung, and Blood Institute (R01HL026441, HL26441)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords
ischemic stroke, T cells, interferon-gamma, cerebral ischemia-reperfusion injury, CD4+ T cells, CD8+ T cells, B cells, leukocyte adhesion, platelet adhesion, cerebral microvasculature, neuroinflammation, thrombosis, infarct size, neurological deficit, Rag1-deficient mice, middle cerebral artery occlusion
MeSH terms
Animals, Blood Pressure, Cell Adhesion, Brain Ischemia, Cerebrovascular Circulation, Interferon-gamma, Male, Mice, Inbred C57BL, Neutrophils, T-Lymphocytes, Reperfusion Injury, Stroke, Mice

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