Role of T lymphocytes and interferon-gamma in ischemic stroke.
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.


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.
Yilmaz
Gokhan
G
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA.
Arumugam
Thiruma V
TV
Stokes
Karen Y
KY
Granger
D Neil
DN
D000818:Animals; D001794:Blood Pressure; D002545:Brain Ischemia / Q000209:etiology*; D002448:Cell Adhesion; D002560:Cerebrovascular Circulation; D007371:Interferon-gamma / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000502:physiology; D015427:Reperfusion Injury / Q000209:etiology; D020521:Stroke / Q000209:etiology*; D013601:T-Lymphocytes / Q000502:physiology*
D007371:Interferon-gamma