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Pathogenic and regulatory T cells, autoimmunity, neuroimmunologyMy laboratory focuses on the mechanism of self-tolerance in autoreactive T cells. Breakdown of self-tolerance leads to induction of autoimmune diseases including Multiple Sclerosis (MS), Rheumatoid Arthritis, and Type 1 Diabetes. To address the question how self-tolerance is maintained in vivo, we have developed humanized transgenic animal models of MS using HLA-DR gene and Central Nervous System (CNS)-specific T cell receptor (TCR) genes isolated from patients with MS. We have found that Th-1 and Th-17 cells expressing the CNS-specific TCR genes derived from MS patients induce experimental autoimmune encephalomyelitis (EAE), an animal model of MS, while the CNS-specific Foxp3+ regulatory T cells suppressed the development of disease. These findings indicate that Foxp3+ regulatory T cells play a pivotal role in suppression of autoimmune diseases including MS. We are currently investigating following research areas. ● Mechanism of differentiation of CNS-specific Foxp3+ regulatory T cells in the thymus and peripheral lymphoid organs. ● Development of CNS-specific Foxp3+regulatory human T cells form human bone marrow stem cells using humanized animal models. ● Role of CNS-specific regulatory T cells in recovery from spinal cord injury. ● Role of bone marrow stem cells in recovery from neurodegenerative diseases. Selected PublicationsGebe JA, Unrath KA, Falk BA, Ito K, Wen L, Daniels TL, Lernmark A, Nepom GT. (2006) Age-dependent loss of tolerance to an immunodominant epitope of glutamic acid decarboxylase in diabetic-prone RIP-B7/DR4 mice. Clin Immunol. 121:294-304. Quandt J.A., Baig M., Yao K., Kawamura K, Huh J., Ludwin S., Bian H.J., Bryant M., Quigley L., Nagy Z., McFarland H.F., Muraro P.A., Martin R., and Ito K. (2004) Unique Phenotypic Clinical and Pathological Features in HLA-DRB1*0401-restricted MBP111-129-specific Humanized TCR Tg mice. J. Exp. Med. 200:223-234.
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