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Lymphocyte Migration in Development of Type 1 Diabetes

1 型糖尿病发展过程中的淋巴细胞迁移

基本信息

批准号：
7169201
负责人：
SARA A MICHIE
金额：
$ 26.58万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-03-01 至 2009-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7169201
关键词：
Adhesions Adult Antigens Autoimmune Diseases Autoimmune Process Autoimmune Responses Autoimmunity Beta Cell Binding Blood Blood Circulation Cell Adhesion Cell Adhesion Molecules Cell Differentiation process Cells Dendritic Cells Development Diabetes Mellitus Effector Cell Endothelial Cells Flow Cytometry Goals Immigration Immunity Immunofluorescence Immunologic Inbred NOD Mice Incidence Inflammation Inflammatory Response Insulin-Dependent Diabetes Mellitus Islets of Langerhans Laboratories Leukocytes Ligands Lymphocyte Mediating Memory Migration Assay Monoclonal Antibodies Neonatal Organism Pancreas Pathogenesis Pathologic Pathway interactions Phase Physiological Population Prevention Production Recruitment Activity Regulation Research Research Personnel Reverse Transcriptase Polymerase Chain Reaction Role Site Staging Staining method Stains Suspension substance Suspensions T-Cell Development T-Lymphocyte Testing Tissues Work autoreactive T cell chemokine chemokine receptor in vivo islet laser capture microdissection lymph nodes member migration response therapeutic target treatment effect

项目摘要

DESCRIPTION (provided by applicant): OBJECTIVES Type 1 diabetes (T1DM) is a T cell mediated autoimmune disease. In the early stages of the autoimmune response, naive autoreactive T cells migrate from blood into pancreatic lymph nodes where they meet Beta cell antigens; memory/effector offspring of these T cells then migrate from blood into islets to initiate the inflammation that leads to Beta cell destruction. The migration of lymphocytes from blood into tissues requires tissue-selective multistep cascades with sequential lymphocyte/endothelial adhesion and activation steps. Our goals are to identify the endothelial adhesion and activating molecules (such as chemokines) that are expressed in pancreatic lymph nodes and islets in the early stages of inflammation, to define the roles of these molecules in lymphocyte recruitment to these sites and in the initiation of the autoimmune response, and to determine which molecules are therapeutic targets for the prevention of T1DM. RESEARCH PLANS AND METHODS We will use tissue section immunohistology, suspension immunofluorescence staining with flow cytometry, and laser capture microdissection (LCM) with RT-PCR to determine which adhesion molecules, chemokines, and chemokine receptors are present in pancreatic lymph nodes (Aim 1) and islets (Aim 2) of nonobese diabetic (NOD) mice in the early stages of the autoimmune process. The physiologic roles of these molecules in the migration of naive autoreactive T cells into pancreatic lymph nodes (Aim 1) and in the production of memory/effector T cells which migrate to islets (Aim 2) will be defined using in vivo lymphocyte migration assays. In Aim 3, we will work closely with Dr. Hugh McDevitt to determine the effects of TNFalpha and anti- TNFalpha on lymphocyte migration pathways and on the development of autoimmunity or tolerance.

描述（由申请人提供）：