Naive CD8+ T cell recruitment and proliferation are dependent on stage of dendritic cell maturation.
Dendritic cells (DC) play a crucial role in controlling the initiation and orientation of antigen (Ag)-specific immune responses. It is widely accepted that optimal T cell priming requires mature DC. Although the molecular events associated with DC activation have been extensively studied, little is known about the consequences of DC maturation on recruitment and expansion of naive T cells. In the present study, we used a model tumor Ag to show that the kinetics of human DC maturation drastically affect the induction of Ag-specific effector CD8(+) T cells. In absence of exogenous cytokines and CD4 help, only DC at early stages of maturation were able to generate high frequencies of CTL. This expansion resulted from both enhanced recruitment and intense proliferation ofT cell precursors and could lead to an increase of up to 1,000-fold in the final number of effector T cells compared to non-matured DC. In our model, larger recruitment of naïve CD8(+) cells did not modify the overall avidity of the Ag-specific T cell population.
Kaiser
Andrew
A
Immuno-Designed Molecules, University of Pierre et Marie Curie Paris, France.
Bercovici
Nadège
N
Abastado
Jean-Pierre
JP
Nardin
Alessandra
A
D000951:Antigens, Neoplasm; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D058965:MART-1 Antigen; D009363:Neoplasm Proteins / Q000032:analysis / Q000378:metabolism; D013997:Time Factors
D000951:Antigens, Neoplasm; D016207:Cytokines; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D007371:Interferon-gamma