کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6117521 1217226 2009 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
TLR-9 signaling and TCR stimulation co-regulate CD8+ T cell-associated PD-1 expression
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی
پیش نمایش صفحه اول مقاله
TLR-9 signaling and TCR stimulation co-regulate CD8+ T cell-associated PD-1 expression
چکیده انگلیسی
Elevated Programmed Death-1 (PD-1) expression can inhibit T cell activity and is a potential barrier to achieving persisting and optimal immunity via therapeutic vaccination. Using a direct lymph node-targeted vaccination procedure that enabled uncoupling of synthetic peptide (signal 1, TCR-mediated) and adjuvant (signal 2, non-TCR-mediated), we evaluated the impact of varied doses of Toll-like receptor (TLR)-9 ligand CpG oligodeoxynucleotide (ODN) adjuvant on epitope-specific CD8+ T cell-associated PD-1 expression. Peptide vaccination without adjuvant yielded CD8+ T cells with significantly elevated PD-1 expression. This conferred impaired function ex vivo, but was reversible by antibody-mediated PD-1 blockade. By comparison, peptide vaccination with escalating doses of CpG ODN adjuvant yielded higher magnitudes of CD8+ T cells with progressively lower PD-1 expression and greater ex vivo function. CpG ODN adjuvant in context of titrated peptide doses for vaccination yielded the lowest overall PD-1 expression levels, demonstrating that fine-tuning both TCR-independent (adjuvant dose) and -dependent (antigen dose) stimuli can synergize to co-regulate PD-1 expression on epitope-specific CD8+ T cells. These data hint at strategies to elicit PD-1low CD8+ T cells using TLR-9 ligand adjuvants, and also shed light on the PD-1-regulated homeostasis of CD8+ T cells.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Immunology Letters - Volume 127, Issue 1, 2 December 2009, Pages 60-67
نویسندگان
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