کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2830705 1163750 2015 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Spontaneously relapsing–remitting experimental autoimmune uveitis in rats allows successful therapeutic oral tolerance induction in ongoing disease
ترجمه فارسی عنوان
واکسیناسیون خودبخودی مجدد یوئیت اتوایمیون تجربی در موش صحرایی باعث القاء موفقیت آمیز تحمل پذیری درمانی در بیماری های جاری می شود
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شناسی مولکولی
چکیده انگلیسی


• We show therapy of relapsing experimental autoimmune uveitis by oral tolerance.
• Oral tolerance can effectively suppress an already activated autoimmune response.
• Combined high- and low-dose oral tolerance ameliorates the primary disease course.

Antigen-specific tolerance induction is a desired therapy for uveitis patients. Our relapsing–remitting rat model of experimental autoimmune uveitis (EAU) induced with IRBP peptide R14 enables us to test the effect of oral tolerance on the prevention of relapsing uveitis. We investigated several peptides overlapping the sequence of R14 for prevention and different doses of R14 for therapy to determine the tolerogenic epitope and the most effective therapeutic regimen for uveitis. Lewis rats were immunized with R14-CFA to induce EAU. Oral tolerance was induced prior to immunization (prevention) or after onset of EAU to prevent relapses (therapy). Therapeutic feeding was performed with high and/or low doses of oral antigen for clonal deletion of effector and induction of regulatory T cells. Uveitis was determined clinically and histologically; mesenteric lymph node (mLN) cells of tolerized rats were tested for surface markers, cytokines and Foxp3 expression. Preventive feeding of R14 and its major epitope R16, but none of the overlapping peptides significantly suppressed EAU and also prevented relapses, irrespective of their pathogenicity. Therapeutic feeding with R14 dramatically reduced relapses, while only the consecutive feeding of high and low-dose R14 had an ameliorating effect on the first course of disease. IL-10-producing T cells from mLN decreased after oral tolerization, and with R14-stimulation in vitro the TCRαβ+/Foxp3+ population increased in the low-dose fed group. No mLN population could be clearly assigned to successful oral tolerance induction during active autoimmune uveitis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Immunology - Volume 63, Issue 2, February 2015, Pages 215–226
نویسندگان
, , ,