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

• Published in: Nature medicine Vol. 11; no. 7; pp. 748 - 756
• Main Authors: Harty, John T, Badovinac, Vladimir P, Messingham, Kelly A N, Jabbari, Ali, Haring, Jodie S
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.07.2005
• Subjects: Animals; Antigens; Cancer immunotherapy; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; CpG Islands; Dendritic cells; Dendritic Cells - immunology; Effector cells; Genotype & phenotype; Immunization, Secondary; Immunologic Memory; Immunological memory; Immunotherapy; Infections; Inflammation; Inflammation - immunology; Inflammation - metabolism; Interferon; Interferon gamma Receptor; Interferon-gamma - metabolism; Listeria monocytogenes - immunology; Listeria monocytogenes - pathogenicity; Lymphocytes; Lymphocytes T; Medical laboratories; Memory cells; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Mutant Strains; Oligonucleotides; Peptides; Phenotypes; Receptors, Interferon - genetics; Receptors, Interferon - metabolism; Spleen; Vaccination; Vaccination - methods; Vaccines; Virulence; γ-Interferon; United States > US; Iowa; Iowa City Iowa
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/nm1257

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.