Characterization of lymphocytes that suppress EAE

抑制 EAE 的淋巴细胞的表征

• 批准号: 8088992
• 负责人: Juan Lafaille
• 金额: $ 39.8万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-02 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8088992
• 关键词: Adjuvant; Antigen-Presenting Cells; Antigens; Apoptosis; Autoimmune Process; Biological; CD28 gene; CD4 Positive T Lymphocytes; Cells; Cellular biology; Characteristics; Chronic; Colitis; Cytokine Receptors; Dendritic Cells; Dependence; Event; Experimental Autoimmune Encephalomyelitis; Frequencies; Funding; Generations; Grant; IL2RA gene; IgE; Image; Immune response; Immune system; Inflammatory; Interleukin-10; Interleukin-2; Knowledge; Lymphocyte; Mediating; Modeling; Multiple Sclerosis; Mus; Myelin Basic Proteins; Pattern; Property; Regulatory T-Lymphocyte; Relative (related person); Role; Signal Transduction; Specificity; Spleen; Structure of parenchyma of lung; T-Cell Receptor; T-Lymphocyte; Testing; Time; Transgenic Mice; Work; allergic response; central nervous system demyelinating disorder; clinical application; cytokine; design; immunogenic; immunoregulation; in vivo; intravital microscopy; migration; prevent; research study; response; two-photon

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.

实验性自身免疫性脑脊髓炎是一种炎症性脱髓鞘