Quantitation of CD8+ T cell expansion, memory, and protective immunity after immunization with peptide-coated dendritic cells.
Dendritic cells (DCs) are potent APCs for naive CD8(+) T cells and are being investigated as vaccine delivery vehicles. In this study, we examine the CD8(+) T cell response to defined peptides from Listeria monocytogenes (LM), lymphocytic choriomeningitis virus, and murine CMV coated singly and in combination onto mature bone marrow-derived DCs (BMDCs). We show that immunization of mice with 2 x 10(5) mature BMDCs coated with multiple MHC class I peptides generates a significant Ag-specific CD8(+) T cell response in both the spleen and nonlymphoid organs. This immunization resulted in a peptide-specific hierarchy in the magnitude of CD8(+) T cell priming and noncoordinate kinetics in response to different peptide epitopes. Kinetics were not exclusively due to specific characteristics of the MHC class I molecule, and were not altered in an Ag-independent manner by concurrent LM infection. Mice immunized with listeriolysin O 91-99-coated BMDCs are protected against high dose challenge with virulent LM. This protection was enhanced by diversifying the memory CD8(+) T cell compartment, even in the absence of a large increase in Ag-specific CD8(+) memory T cells.
Hamilton
Sara E
SE
Interdisciplinary Program in Immunology and Department of Microbiology, University of Iowa, Iowa City 52242, USA.
Harty
John T
JT
D000818:Animals; D017951:Antigen Presentation; D001426:Bacterial Proteins / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D001427:Bacterial Toxins; D001854:Bone Marrow Cells / Q000276:immunology / Q000382:microbiology; D016026:Bone Marrow Transplantation; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000382:microbiology; D002455:Cell Division / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000382:microbiology / Q000637:transplantation*; D018984:Epitopes, T-Lymphocyte / Q000032:analysis / Q000276:immunology; D005260:Female; D006183:H-2 Antigens / Q000276:immunology / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000008:administration & dosage / Q000276:immunology / Q000378:metabolism; D006460:Hemolysin Proteins; D064532:Histocompatibility Antigen H-2D; D007113:Immunity, Innate; D007156:Immunologic Memory; D007275:Injections, Intravenous; D007700:Kinetics; D008088:Listeriosis / Q000276:immunology / Q000517:prevention & control; D008099:Liver / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D064532:Histocompatibility Antigen H-2D; D009842:Oligopeptides; C038705:hlyA protein, Listeria monocytogenes