title: Stroke induces a rapid adaptive autoimmune response to novel neuronal antigens.
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.
authors.affiliation: Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Sterling B
authors.initials: SB
authors.lastname: Ortega
authors.affiliation: Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Noorbhai
authors.affiliation: Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Katie
authors.initials: K
authors.lastname: Poinsatte
authors.affiliation: Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Kong
authors.affiliation: Department of Neuroscience, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Anderson
authors.affiliation: Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Monson
authors.affiliation: Department of Neurology and Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Stowe
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D006801:Humans; D008198:Lymph Nodes; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009186:Myelin Sheath / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry; D020127:Recovery of Function; D013154:Spleen / Q000473:pathology; D020521:Stroke / Q000276:immunology*
chemical_list: D000941:Antigens; D010455:Peptides