Quantitation of CD8+ T Cell Expansion, Memory, and Protective Immunity After Immunization with Peptide-Coated Dendritic Cells

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 × 105 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.