CD4+ CD25+ regulatory T cells prevent type 1 diabetes preceded by dendritic cell-dominant invasive insulitis by affecting chemotaxis and local invasiveness of dendritic cells

The Journal of Immunology : Official Journal of the American Association of Immunologists
Mi-Heon LeeChih-Pin Liu

Abstract

Development of type 1 diabetes (T1D) is preceded by invasive insulitis. Although CD4(+)CD25(+) regulatory T cells (nTregs) induce tolerance that inhibits insulitis and T1D, the in vivo cellular mechanisms underlying this process remain largely unclear. Using an adoptive transfer model and noninvasive imaging-guided longitudinal analyses, we found nTreg depletion did not affect systemic trafficking and tissue localization of diabetogenic CD4(+) BDC2.5 T (BDC) cells in recipient mice prior to development of T1D. In addition, neither the initial expansion/activation of BDC cells nor the number of CD11c(+) or NK cells in islets and pancreatic lymph nodes were altered. Unexpectedly, our results showed nTreg depletion led to accelerated invasive insulitis dominated by CD11c(+) dendritic cells (ISL-DCs), not BDC cells, which stayed in the islet periphery. Compared with control mice, the phenotype of ISL-DCs and their ability to stimulate BDC cells did not change during invasive insulitis development. However, ISL-DCs from nTreg-deficient recipient mice showed increased in vitro migration toward CCL19 and CCL21. These results demonstrated invasive insulitis dominated by DCs, not CD4(+) T cells, preceded T1D onset in the absence of nTre...Continue Reading

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Citations

May 31, 2012·Proceedings of the National Academy of Sciences of the United States of America·Ding WangChih-Pin Liu
Feb 9, 2016·The Journal of Clinical Investigation·Scott J PattersonMegan K Levings
Jul 22, 2011·Stem Cells International·Marta Isabel Pereira, Artur Paiva
Mar 2, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yi-Guang ChenDavid V Serreze

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