کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8739516 | 1592259 | 2018 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Low CD25 on autoreactive Tregs impairs tolerance via low dose IL-2 and antigen delivery
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موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ایمونولوژی
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چکیده انگلیسی
Dendritic cell (DC)-mediated T cell tolerance deficiencies contribute to the pathogenesis of autoimmune diseases such as type 1 diabetes. Delivering self-antigen to dendritic-cell inhibitory receptor-2 (DCIR2)+ DCs can delay but not completely block diabetes development in NOD mice. These DCIR2-targeting antibodies induce tolerance via deletion and anergy, but do not increase islet-specific Tregs. Because low-dose IL-2 (LD-IL-2) administration can preferentially expand Tregs, we tested whether delivering islet-antigen to tolerogenic DCIR2+ DCs along with LD-IL-2 would boost islet-specific Tregs and further block autoimmunity. But, surprisingly, adding LD-IL-2 did not increase efficacy of DC-targeted antigen to inhibit diabetes. Here we show the effects of LD-IL-2, with or without antigen delivery to DCIR2+ DCs, on both polyclonal and autoreactive Treg and conventional T cells (Tconv). As expected, LD-IL-2 increased total Tregs, but autoreactive Tregs required both antigen and IL-2 stimulation for optimal expansion. Also, islet-specific Tregs had lower CD25 expression and IL-2 sensitivity, while islet-specific Tconv had higher CD25 expression, compared to polyclonal populations. LD-IL-2 increased activation and expansion of Tconv, and was more pronounced for autoreactive cells after treatment with IL-2Â +Â islet-antigen. Therefore, LD-IL-2 therapy, especially when combined with antigen stimulation, may not optimally activate and expand antigen-specific Tregs in chronic autoimmune settings.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Autoimmunity - Volume 90, June 2018, Pages 39-48
Journal: Journal of Autoimmunity - Volume 90, June 2018, Pages 39-48
نویسندگان
Chie Hotta-Iwamura, Charles Benck, William D. Coley, Yi Liu, Yongge Zhao, Juan A. Quiel, Kristin V. Tarbell,