Accelerated CD8+ T-cell memory and prime-boost response after dendritic-cell vaccination

Nat Med. 2005 Jul;11(7):748-56. doi: 10.1038/nm1257. Epub 2005 Jun 12.

Abstract

Efficient boosting of memory T-cell numbers to protective levels generally requires a relatively long interval between immunizations. Decreasing this interval could be crucial in biodefense and cancer immunotherapy, in which rapid protective responses are essential. Here, we show that vaccination with peptide-coated dendritic cells (DCs) generated CD8+ T cells with the phenotype and function of memory cells within 4-6 d. These early memory CD8+ T cells underwent vigorous secondary expansion in response to a variety of booster immunizations, leading to elevated numbers of effector and memory T cells and enhanced protective immunity. Coinjection of CpG oligodeoxynucleotides, potent inducers of inflammation that did not alter the duration of DC antigen display, prevented the rapid generation of memory T cells in wild-type mice but not in mice lacking the interferon (IFN)-gamma receptor. These data show that DC vaccination stimulates a pathway of accelerated generation of memory T cells, and suggest that events of inflammation, including the action of IFN-gamma on the responding T cells, control the rate of development of memory CD8+ T cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CpG Islands
  • Dendritic Cells / immunology*
  • Immunization, Secondary*
  • Immunologic Memory*
  • Inflammation / immunology
  • Inflammation / metabolism
  • Interferon-gamma / metabolism*
  • Listeria monocytogenes / immunology
  • Listeria monocytogenes / pathogenicity
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Receptors, Interferon / genetics
  • Receptors, Interferon / metabolism
  • Vaccination / methods

Substances

  • Receptors, Interferon
  • interferon gamma receptor
  • Interferon-gamma