Journal article
Stroke induces a rapid adaptive autoimmune response to novel neuronal antigens
Discovery medicine, Vol.19(106), pp.381-392
05/2015
PMCID: PMC4692161
PMID: 26105701
Abstract
Stroke affects millions of people worldwide every year. Despite this prevalence, mechanisms of long-term injury and repair within the ischemic brain are still understudied. Sterile inflammation occurs in the injured brain after stroke, with damaged tissue exposing central nervous system (CNS)-derived antigen that could initiate potential autoimmune responses. We used a standard immunology-based recall response assay for murine immune cells, isolated from the cervical lymph nodes and spleen after transient stroke, to determine if stroke induces autoreactivity to CNS target antigens. Our assays included novel neuronal peptides, in addition to myelin-, nuclear-, glial-, and endothelial-derived peptides. Autoimmune responses to an antigen were considered positive based on proliferation and activation over non-stimulated conditions. Stroke induced a significant increase in autoreactive CD4+ and CD8+ T cells, as well as autoreactive CD19+ B cells, as early as 4 days after stroke onset. Mice with large infarct volumes exhibited early T and B cell autoreactivity to NR2A, an NMDA receptor subunit, in cells isolated from lymph nodes but not spleen. Mice with small infarct volumes exhibited high autoreactivity to MAP2, a dendritic cytoskeletal protein, as well as myelin-derived peptides. This autoimmunity was maintained through 10 days post-stroke in both lymph nodes and spleen for all lymphocyte subsets. Sham surgery also induced early autoreactive B cell responses to MAP2 and myelin. Based on these observations, we hypothesize that stroke induces a secondary, complex, and dynamic autoimmune response to neuronal antigens with the potential to potentiate, or perhaps even ameliorate, long-term neuroinflammation.
Details
- Title: Subtitle
- Stroke induces a rapid adaptive autoimmune response to novel neuronal antigens
- Creators
- Sterling B Ortega - Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX 75390, USAIbrahim Noorbhai - Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX 75390, USAKatie Poinsatte - Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX 75390, USAXiangmei Kong - Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX 75390, USAAshley Anderson - Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX 75390, USANancy L Monson - Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX 75390, USAAnn M Stowe - Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX 75390, USA
- Resource Type
- Journal article
- Publication Details
- Discovery medicine, Vol.19(106), pp.381-392
- Publisher
- United States
- PMID
- 26105701
- PMCID
- PMC4692161
- ISSN
- 1539-6509
- eISSN
- 1944-7930
- Grant note
- R01 NS088555 / NINDS NIH HHS NS088555 / NINDS NIH HHS
- Language
- English
- Date published
- 05/2015
- Academic Unit
- Pathology
- Record Identifier
- 9984065494502771
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