4.8 Article

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

Journal

NATURE MEDICINE
Volume 11, Issue 7, Pages 748-756

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/nm1257

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Funding

  1. NIAID NIH HHS [T32AI007511, AI42767, AI50073, AI46653, T32AI0726] Funding Source: Medline

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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.

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