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Regulation of CD8+ T cell‐associated Programmed Death‐1 (PD‐1) expression by antigen‐dependent and ‐independent signaling
Author(s) -
Wong Raymond,
Smith Kent,
Tam Victor,
Meisenberg Brenna,
Quach Angeline,
Carillo Mayra,
Bot Adrian
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1076.4
Subject(s) - cytotoxic t cell , antigen , biology , immune system , cd8 , t cell , microbiology and biotechnology , epitope , t cell receptor , immunology , in vitro , biochemistry
PD‐1/PD‐1 ligand interaction regulates immune homeostasis and is a potential barrier to optimal T cell activity against viruses and tumors. Using a lymph node‐targeted immunization approach, we evaluated the impact of antigen‐dependent and ‐independent signaling on the phenotype of CD8+ T cells, with focus on expression of the inhibitory receptor PD‐1. The levels of antigen exposure and co‐stimulation provided by CpG oligodeoxynucleotide (ODN) adjuvant, respectively, had striking and opposite effects on PD‐1 acquisition by epitope‐specific CD8+ T cells (∼5 to 65% positive). Elevated PD‐1 expression was associated with decreased functionality on a cell‐for‐cell basis, which was at least partly reversible by antibody‐mediated PD‐1 blockade. Low antigen exposure in context of an optimal immune co‐stimulatory signal – via peptide + CpG ODN or DNA plasmid immunization – yielded low PD‐1‐expressing central and peripheral memory cells with substantial proliferation and differentiation potential upon subsequent antigen stimulation. These findings shed light on the distinctive mechanism of action of DNA and peptide vaccines and, in general, the homeostasis of CD8+ T cells via induction of an inhibitor receptor. Funding for this research was provided by MannKind Corporation.