Brain ischemia induces diversified neuroantigen-specific T-Cell responses that exacerbate brain injury

Wei Na Jin, Rayna Gonzales, Yan Feng, Kristofer Wood, Zhi Chai, Jing Fei Dong, Antonio La Cava, Fu Dong Shi, Qiang Liu

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Background and Purpose-Autoimmune responses can occur when antigens from the central nervous system are presented to lymphocytes in the periphery or central nervous system in several neurological diseases. However, whether autoimmune responses emerge after brain ischemia and their impact on clinical outcomes remains controversial. We hypothesized that brain ischemia facilitates the genesis of autoimmunity and aggravates ischemic brain injury. Methods-Using a mouse strain that harbors a transgenic T-cell receptor to a central nervous system antigen, MOG35-55 (myelin oligodendrocyte glycoprotein) epitope (2D2), we determined the anatomic location and involvement of antigenpresenting cells in the development of T-cell reactivity after brain ischemia and how T-cell reactivity impacts stroke outcome. Transient middle cerebral artery occlusion and photothrombotic stroke models were used in this study. We also quantified the presence and status of T cells from brain slices of ischemic patients. Results-By coupling transfer of labeled MOG35-55-specific (2D2) T cells with tetramer tracking, we show an expansion in reactivity of 2D2 T cells to MOG91-108 and MOG103-125 in transient middle cerebral artery occlusion and photothrombotic stroke models. This reactivity and T-cell activation first occur locally in the brain after ischemia. Also, microglia act as antigen-presenting cells that effectively present MOG antigens, and depletion of microglia ablates expansion of 2D2 reactive T cells. Notably, the adoptive transfer of neuroantigen-experienced 2D2 T cells exacerbates Th1/Th17 responses and brain injury. Finally, T-cell activation and MOG-specific T cells are present in the brain of patients with ischemic stroke. Conclusions-Our findings suggest that brain ischemia activates and diversifies T-cell responses locally, which exacerbates ischemic brain injury.

Original languageEnglish (US)
Pages (from-to)1471-1478
Number of pages8
JournalStroke
Volume49
Issue number6
DOIs
StatePublished - Jan 1 2018

Keywords

  • T-cells
  • adaptive immunity
  • antigen presentation
  • brain injury
  • brain ischemia

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

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    Jin, W. N., Gonzales, R., Feng, Y., Wood, K., Chai, Z., Dong, J. F., La Cava, A., Shi, F. D., & Liu, Q. (2018). Brain ischemia induces diversified neuroantigen-specific T-Cell responses that exacerbate brain injury. Stroke, 49(6), 1471-1478. https://doi.org/10.1161/str.49.suppl