Charaterizing lymphocytes that suppress Experimental Autoimmune Encephalomyelitis

表征抑制实验性自身免疫性脑脊髓炎的淋巴细胞

• 批准号: 7208963
• 负责人: Juan Lafaille
• 金额: $ 36.05万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7208963
• 关键词: Biological; CD28 gene; CD4 Positive T Lymphocytes; Cells; Characteristics; Cytokine Receptors; Dependence; Development; Effector Cell; Event; Experimental Autoimmune Encephalomyelitis; Generations; Genotype; IL2RA gene; Incidence; Inflammatory; Interleukin-10; Interleukin-2; Knowledge; Lymphocyte; MHC Class II Genes; Modeling; Monitor; Multiple Sclerosis; Mus; Myelin Basic Proteins; Numbers; Onset of illness; Pattern; Personal Satisfaction; Population; Production; Property; Research Personnel; Role; Signal Transduction; System; T-Cell Receptor; T-Lymphocyte; Transgenic Mice; central nervous system demyelinating disorder; clinical application; cytokine; design; immunoregulation; in vivo; prevent; research study

DESCRIPTION (provided by applicant): Experimental autoimmune encephalomyelitis is an inflammatory demyelinating disease of the central nervous system (CNS) studied as a model of multiple sclerosis. Mice which harbor a monoclonal myelin basic protein (MBP)-specific ab T cell compartment develop EAE spontaneously. EAE can be prevented in these mice by the administration of a small number of polyclonal CD4+ T cells (regulatory T cells or T-reg) belonging to either the CD4+CD25+ or the CD4+CD25- T cell subpopulations. The biological impact of T-reg administration is large, and, therefore, so is its potential for clinical application, yet many important properties of T-reg cells that control spontaneous EAE remain poorly understood. This application focuses on key events involved in immunoregulation of spontaneous EAE in MBP-specific T cell receptor transgenic mice. In Aim 1, we will assess the role of the cytokines, cytokine receptors and co-stimulatory molecules IL-2, CD25, IL-10, TGF-b and CD28 in the generation, survival and function of T-reg. A better knowledge of T-reg dependence on these cytokines and co-stimulatory signals may enhance the potential of in vivo manipulation of immunoregulatory T cells. In Aim 2, we will investigate the MHC restriction of regulatory T cells. The characteristics of MHC restriction of T-reg cells may help in the design of strategies to purify these cells out of the total CD4+ T cell compartment.

描述（申请人提供）：实验性自身免疫性脑脊髓炎是一种中枢神经系统（CNS）炎性脱髓鞘疾病，作为多发性硬化症模型进行研究。携带单克隆髓鞘碱性蛋白（MBP）特异性ab T细胞区室的小鼠自发发生EAE。在这些小鼠中，通过给予少量属于CD 4 + CD 25+或CD 4 + CD 25- T细胞亚群的多克隆CD 4 + T细胞（调节性T细胞或T-reg）可以预防EAE。T-reg给药的生物学影响很大，因此其临床应用潜力也很大，但对控制自发性EAE的T-reg细胞的许多重要特性仍知之甚少。本申请集中于MBP特异性T细胞受体转基因小鼠中自发性EAE的免疫调节所涉及的关键事件。在目的1中，我们将评估细胞因子，细胞因子受体和共刺激分子IL-2，CD 25，IL-10，TGF-β和CD 28在T-reg的产生，存活和功能中的作用。更好地了解T-reg对这些细胞因子和共刺激信号的依赖性，可能会增强免疫调节性T细胞的体内操作的潜力。在目标2中，我们将研究调节性T细胞的MHC限制。T-reg细胞的MHC限制的特性可能有助于设计从总CD 4 + T细胞区室中纯化这些细胞的策略。

项目成果

Two-photon laser scanning microscopy imaging of intact spinal cord and cerebral cortex reveals requirement for CXCR6 and neuroinflammation in immune cell infiltration of cortical injury sites.

• DOI: 10.1016/j.jim.2009.09.007
• 发表时间: 2010-01-31
• 期刊: JOURNAL OF IMMUNOLOGICAL METHODS
• 影响因子: 2.2
• 作者: Kim, Jiyun V.;Jiang, Ning;Tadokoro, Carlos E.;Liu, Liping;Ransohoff, Richard M.;Lafaille, Juan J.;Dustin, Michael L.
• 通讯作者: Dustin, Michael L.

Regulatory T cells inhibit stable contacts between CD4+ T cells and dendritic cells in vivo.

调节性T细胞在体内抑制CD4+ T细胞和树突状细胞之间的稳定接触。

• DOI: 10.1084/jem.20050783
• 发表时间: 2006-03-20
• 期刊: JOURNAL OF EXPERIMENTAL MEDICINE
• 影响因子: 15.3
• 作者: Tadokoro, Carlos E;Shakhar, Guy;Shen, Shiqian;Ding, Yi;Lino, Andreia C;Maraver, Antonio;Lafaille, Juan J;Dustin, Michael L
• 通讯作者: Dustin, Michael L

Swift entry of myelin-specific T lymphocytes into the central nervous system in spontaneous autoimmune encephalomyelitis.

• DOI: 10.4049/jimmunol.181.7.4648
• 发表时间: 2008-10-01
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Furtado GC;Marcondes MC;Latkowski JA;Tsai J;Wensky A;Lafaille JJ
• 通讯作者: Lafaille JJ

Regulatory CD4(+) T cells expressing endogenous T cell receptor chains protect myelin basic protein-specific transgenic mice from spontaneous autoimmune encephalomyelitis.

• DOI: 10.1084/jem.188.10.1883
• 发表时间: 1998-11-16
• 期刊: The Journal of experimental medicine