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TLR-9 signaling and TCR stimulation co-regulate CD8+ T cell-associated PD-1 expression by Raymond M. Wong; Kent A. Smith; Victor L. Tam; Robb R. Pagarigan; Brenna L. Meisenburg; Angeline M. Quach; Mayra A. Carrillo; Zhiyong Qiu; Adrian I. Bot is a Immunology and Microbiology article available to read on EtoBox.

What is TLR-9 signaling and TCR stimulation co-regulate CD8+ T cell-associated PD-1 expression about?

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 nodetargeted 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-spe

Who reads TLR-9 signaling and TCR stimulation co-regulate CD8+ T cell-associated PD-1 expression?

Author

Raymond M. Wong; Kent A. Smith; Victor L. Tam; Robb R. Pagarigan; Brenna L. Meisenburg; Angeline M. Quach; Mayra A. Carrillo; Zhiyong Qiu; Adrian I. Bot

Publisher

Elsevier Science; Elsevier ; Elsevier BV (ISSN 0165-2478)

Published

2009

Language

EN

Field

Immunology and Microbiology (Life Sciences)