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1型糖尿病患者CD4记忆性T细胞中IL-2R信号传导减弱是内在的，且依赖于激活状态。

Attenuated IL-2R signaling in CD4 memory T cells of T1D subjects is intrinsic and dependent on activation state.

作者信息

Schwedhelm Katharine, Thorpe Jerill, Murray Sara A, Gavin Marc, Speake Cate, Greenbaum Carla, Cerosaletti Karen, Buckner Jane, Long S Alice

机构信息

Translational Research Program, Benaroya Research Institute, Seattle, WA, USA.

Systems Immunology Program, Benaroya Research Institute, Seattle, WA, USA.

出版信息

Clin Immunol. 2017 Aug;181:67-74. doi: 10.1016/j.clim.2017.06.004. Epub 2017 Jun 20.

DOI:10.1016/j.clim.2017.06.004
PMID:28645874
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5564451/
Abstract

The IL-2/IL-2R pathway is implicated in type 1 diabetes (T1D). While its role in regulatory T cell (Treg) biology is well characterized, mechanisms that influence IL-2 responses in effector T cells (Teff) are less well understood. We compared IL-2 responses in 95 healthy control and 98 T1D subjects. In T1D, low IL-2 responsiveness was most pronounced in memory Teff. Unlike Treg, CD25 expression did not influence the Teff responses. Reduced IL-2 responses in memory Teff were not rescued by resting, remained lower after activation and proliferation, and were absent in type 2 diabetes. Comparing basal IL-2 responses in resting versus activated cells, memory Teff displayed lower, but more sustained, responses to IL-2 overtime. These results suggest that T1D-associated defects in the Teff compartment are due to intrinsic factors related to activation. Evaluation of both Teff and Treg IL-2R signaling defects in T1D subjects may inform selection of therapies.

摘要

白细胞介素-2/白细胞介素-2受体（IL-2/IL-2R）信号通路与1型糖尿病（T1D）有关。虽然其在调节性T细胞（Treg）生物学中的作用已得到充分表征，但影响效应T细胞（Teff）中IL-2反应的机制尚不清楚。我们比较了95名健康对照者和98名T1D患者的IL-2反应。在T1D患者中，低IL-2反应性在记忆性Teff中最为明显。与Treg不同，CD25表达不影响Teff反应。记忆性Teff中IL-2反应降低不能通过静息恢复，在激活和增殖后仍较低，且在2型糖尿病中不存在。比较静息细胞与激活细胞的基础IL-2反应，记忆性Teff对IL-2的反应随时间推移较低，但更持久。这些结果表明，Teff区室中与T1D相关的缺陷是由于与激活相关的内在因素。评估T1D患者中Teff和Treg的IL-2R信号缺陷可能有助于治疗方案的选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/860c/5564451/8d42a378464d/nihms888521f6.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/860c/5564451/8d42a378464d/nihms888521f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/860c/5564451/5c167ee8c430/nihms888521f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/860c/5564451/2527bc279292/nihms888521f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/860c/5564451/27bf801043e1/nihms888521f3.jpg
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