کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2832298 1163834 2007 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A novel multimeric form of FasL modulates the ability of diabetogenic T cells to mediate type 1 diabetes in an adoptive transfer model
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
پیش نمایش صفحه اول مقاله
A novel multimeric form of FasL modulates the ability of diabetogenic T cells to mediate type 1 diabetes in an adoptive transfer model
چکیده انگلیسی

Activation induced cell death (AICD) via Fas/FasL is the primary homeostatic molecular mechanism employed by the immune system to control activated T-cell responses and promote tolerance to self-antigens. We herein investigated the ability of a novel multimeric form of FasL chimeric with streptavidin (SA-FasL) having potent apoptotic activity to induce apoptosis in diabetogenic T cells and modulate insulin-dependent type 1 diabetes (IDDM) in an adoptive transfer model. Diabetogenic splenocytes from NOD/Lt females were co-cultured in vitro with SA-FasL, SA control protein, or alone without protein, and adoptively transferred into NOD/Lt-Rag1null recipients for diabetes development. All animals receiving control (Alone: n = 16 or SA: n = 17) cells developed diabetes on average by 6 weeks, whereas animals receiving SA-FasL-treated (n = 25) cells exhibited significantly delayed progression (p < .001) and decreased incidence (70%). This effect was associated with an increase in CD4+CD25+ T cells and correlated with FoxP3 expression in pancreatic lymph nodes. Extracorporeal treatment of peripheral blood lymphocytes using SA-FasL during disease onset represents a novel approach that may alter the ability of pathogenic T cells to mediate diabetes and have therapeutic utility in clinical management of IDDM.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Immunology - Volume 44, Issue 11, April 2007, Pages 2884–2892
نویسندگان
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