Role of T lymphocytes and interferon-gamma in ischemic stroke

Yilmaz, Gokhan, Arumugam, Thiruma V., Stokes, Karen Y. and Granger, D. Neil (2006) Role of T lymphocytes and interferon-gamma in ischemic stroke. Circulation, 113 17: 2105-2112. doi:10.1161/CIRCULATIONAHA.105.593046

Author Yilmaz, Gokhan
Arumugam, Thiruma V.
Stokes, Karen Y.
Granger, D. Neil
Title Role of T lymphocytes and interferon-gamma in ischemic stroke
Formatted title
Role of T Lymphocytes and Interferon-γ in Ischemic Stroke
Journal name Circulation   Check publisher's open access policy
ISSN 0009-7322
Publication date 2006-05
Sub-type Article (original research)
DOI 10.1161/CIRCULATIONAHA.105.593046
Volume 113
Issue 17
Start page 2105
End page 2112
Total pages 8
Place of publication Baltimore, MD, United States
Publisher Lippincott Williams & Wilkins
Language eng
Formatted 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-γ (IFN-γ) 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-γ 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-γ. 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-γ-/-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-γ-/- 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-γ plays a pivotal role in stroke-induced inflammatory responses, T lymphocytes appear to be a minor source of this cytokine.
Keyword Cerebral ischemia
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
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School of Biomedical Sciences Publications
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Created: Tue, 17 Nov 2009, 12:22:57 EST