Rinsho Shinkeigaku (Clinical Neurology)

The 51st Annual Meeting of the Japanese Society of Neurology

Role of T lymphocytes in ischemic brain injury

Takashi Shichita, M.D., PhD.1)2), Fumie Konoeda, M.D., PhD.1)3) and Akihiko Yoshimura, PhD.1)

1)Department of Microbiology and Immunology, School of Medicine, Keio University
2)Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University
3)Department of Neurology, School of Medicine, Keio University

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.
Full Text of this Article in Japanese PDF (317K)

(CLINICA NEUROL, 50: 878|880, 2010)
key words: Brain ischemia, T lymphocyte, IL-23, IL-17, γδT lymphocyte

(Received: 21-May-10)