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标题：Imaging the emergence and natural progression of spontaneous autoimmune diabetes
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作者：James F. Mohan ; Rainer H. Kohler ; Jonathan A. Hill 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2017
卷号：114
期号：37
页码：E7776-E7785
DOI：10.1073/pnas.1707381114
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Type 1 diabetes in the nonobese diabetic mouse stems from an infiltration of the pancreatic islets by a mixed population of immunocytes, which results in the impairment and eventual destruction of insulin-producing β-cells. Little is known about the dynamics of lymphocyte movement in the pancreas during disease progression. Using advanced intravital imaging approaches and newly created reporter mice ( Flt3-BFP2 , Mertk-GFP-DTR , Cd4-tdTomato , Cd8a-tdTomato ), we show that the autoimmune process initiates first with a T cell infiltration into the islets, where they have restricted mobility but reside and are activated in apposition to CX3CR1⁺ macrophages. The main expansion then occurs in the connective tissue outside the islet, which remains more or less intact. CD4⁺ and CD8⁺ T cells, Tregs, and dendritic cells (DCs) are highly mobile, going along microvascular tracks, while static macrophages (MF) form a more rigid structure, often encasing the islet cell mass. Transient cell–cell interactions are formed between T cells and both MFs and DCs, but also surprisingly between MFs and DCs themselves, possibly denoting antigen transfer. In later stages, extensive islet destruction coincides with preferential antigen presentation to, and activation of, CD8⁺ T cells. Throughout the process, Tregs patrol the active compartments, consistent with the notion that they control the activation of many cell types.
关键词：diabetes ; autoimmunity ; immunoregulation