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标题：Population dynamics of islet-infiltrating cells in autoimmune diabetes
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作者：Angela M. Magnuson ; Greg M. Thurber ; Rainer H. Kohler 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：2015
卷号：112
期号：5
页码：1511-1516
DOI：10.1073/pnas.1423769112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceIn many autoimmune diseases, self-reactive lymphocytes lead to immunocyte infiltration in the target tissue, whose evolution over time is regulated. Such lesions can be well-tolerated and lead to minimal damage, or have more drastic consequences. We show here, for the insulitis of the nonobese diabetic (NOD) mouse model of autoimmune diabetes, that the autoimmune infiltrate is an open and dynamic cell population, with a high turnover and constant reseeding with fresh cells coming from the general lymphoid circulation; this implies that such a lesion is susceptible to extraneous events and influences, which could either provoke overt disease or instill stronger immunosuppression. Type-1 diabetes in the nonobese diabetic (NOD) mouse starts with an insulitis stage, wherein a mixed population of leukocytes invades the pancreas, followed by overt diabetes once enough insulin-producing {beta}-cells are destroyed by invading immunocytes. Little is known of the dynamics of lymphocyte movement into the pancreas during disease progression. We used the Kaede transgenic mouse, whose photoconvertible fluorescent reporter permits noninvasive labeling and subsequent tracking of immunocytes, to investigate pancreatic infiltrate dynamics and the requirement for antigen specificity during progression of autoimmune diabetes in the unmanipulated NOD mouse. Our results indicate that the insulitic lesion is very open with constant cell influx and active turnover, predominantly of B and T lymphocytes, but also CD11b+c+ myeloid cells. Both naive- and memory-phenotype lymphocytes trafficked to the insulitis, but Foxp3+ regulatory T cells circulated less than their conventional CD4+ counterparts. Receptor specificity for pancreatic antigens seemed irrelevant for this homing, because similar kinetics were observed in polyclonal and antigen-specific transgenic contexts. This "open" configuration was also observed after reversal of overt diabetes by anti-CD3 treatment. These results portray insulitis as a dynamic lesion at all stages of disease, continuously fed by a mixed influx of immunocytes, and thus susceptible to evolve over time in response to immunologic or environmental influences.
关键词：Treg ; cell tracer ; reporter