title: [Role of T lymphocytes in ischemic brain injury].
abstract: Recently, inflammation has been implicated in the progression of cerebral ischemic injury. Especially, T lymphocytes have been shown to infiltrate into the ischemic brain 24 hours after the onset, however, the function and specific subpopulation of these infiltrated T lymphocytes have not been fully understood. By using cytokine-deficient mice with transient focal ischemia model, we have shown that IL-23 and IL-17 but not IL-6 or IFN-γ play pivotal roles in the ischemic brain injury. We found that IL-23, which was mainly produced from infiltrated macrophages, induced IL-17-producing T lymphocytes in the ischemic brain. IL-23 and IL-17 expression increased 1 day or 3 day after ischemic injury, respectively, and promoted inflammatory responses by increasing the expression of neurotoxic factors. To our surprise, IL-17 was mainly produced by γδT lymphocytes, but not helper T cells. Based on these findings, we have tried to develop new therapeutic strategy for the progression of brain infarction. We found that administration of FTY720 (Fingolimod) and antibody against γδT lymphocytes attenuated ischemic brain damage. Furthermore, antibody against p40 which neutralizes both IL-23 and IL-12 simultaneously was also effective. Therefore, anti-cytokine therapy will be applicable for neuroprotection in the delayed phase of brain ischemia.
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Keio University.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shichita
authors.forename: Fumie
authors.initials: F
authors.lastname: Konoeda
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshimura
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology / Q000627:therapeutic use; D002545:Brain Ischemia / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D003352:Corynebacterium / Q000276:immunology / Q000502:physiology; D016207:Cytokines; D018450:Disease Progression; D000068876:Fingolimod Hydrochloride; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D020381:Interleukin-17 / Q000502:physiology; D053759:Interleukin-23 / Q000502:physiology; D051379:Mice; D058990:Molecular Targeted Therapy; D011409:Propylene Glycols / Q000494:pharmacology / Q000627:therapeutic use; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
chemical_list: D057134:Antibodies, Neutralizing; D016207:Cytokines; D018836:Inflammation Mediators; D020381:Interleukin-17; D053759:Interleukin-23; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine