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Quantitation of CD8+ T cell expansion, memory, and protective immunity after immunization with peptide-coated dendritic cells
Journal article   Peer reviewed

Quantitation of CD8+ T cell expansion, memory, and protective immunity after immunization with peptide-coated dendritic cells

Sara E Hamilton and John T Harty
The Journal of immunology (1950), Vol.169(9), pp.4936-4944
11/01/2002
DOI: 10.4049/jimmunol.169.9.4936
PMID: 12391206

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Abstract

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.
CD8-Positive T-Lymphocytes - cytology Lung - microbiology Injections, Intravenous Dendritic Cells - immunology Liver - microbiology Histocompatibility Antigen H-2D Listeriosis - prevention & control Lung - cytology Liver - immunology Antigen Presentation Bacterial Toxins Cell Division - immunology Bone Marrow Cells - immunology Bone Marrow Transplantation Listeriosis - immunology Female Bacterial Proteins - immunology Epitopes, T-Lymphocyte - immunology CD8-Positive T-Lymphocytes - microbiology Heat-Shock Proteins - administration & dosage Epitopes, T-Lymphocyte - analysis H-2 Antigens - metabolism Hemolysin Proteins Lymphocyte Activation Heat-Shock Proteins - metabolism Oligopeptides - immunology Oligopeptides - metabolism Immunity, Innate Bacterial Proteins - administration & dosage Heat-Shock Proteins - immunology H-2 Antigens - immunology Animals Bone Marrow Cells - microbiology Dendritic Cells - microbiology Lymphocyte Count Bacterial Proteins - metabolism Immunologic Memory Liver - cytology Mice Mice, Inbred BALB C Oligopeptides - administration & dosage Kinetics CD8-Positive T-Lymphocytes - immunology Dendritic Cells - transplantation Lung - immunology

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