Accelerated CD8+ T-cell memory and prime-boost response after dendritic-cell vaccination.
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.
Badovinac
Vladimir P
VP
Department of Microbiology, 3-512 Bowen Science Building, 51 Newton Road, University of Iowa, Iowa City, Iowa 52240, USA.
Messingham
Kelly A N
KA
Jabbari
Ali
A
Haring
Jodie S
JS
Harty
John T
JT
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018899:CpG Islands; D003713:Dendritic Cells / Q000276:immunology*; D007117:Immunization, Secondary; D007156:Immunologic Memory; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism*; D008089:Listeria monocytogenes / Q000276:immunology / Q000472:pathogenicity; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D017471:Receptors, Interferon / Q000235:genetics / Q000378:metabolism; D014611:Vaccination / Q000379:methods; D000096743:Interferon gamma Receptor
D007371:Interferon-gamma; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor