TY - JOUR
T1 - Splenic CD8α+ dendritic cells undergo rapid programming by cytosolic bacteria and inflammation to induce protective CD8+ T-cell memory
AU - Campisi, Laura
AU - Soudja, Saidi M.Homa
AU - Cazareth, Julie
AU - Bassand, Delphine
AU - Lazzari, Anne
AU - Brau, Frédéric
AU - Narni-Mancinelli, Emilie
AU - Glaichenhaus, Nicolas
AU - Geissmann, Frédéric
AU - Lauvau, Grégoire
N1 - Copyright:
Copyright 2011 Elsevier B.V., All rights reserved.
PY - 2011/6
Y1 - 2011/6
N2 - Memory CD8+ T lymphocytes are critical effector cells of the adaptive immune system mediating long-lived pathogen-specific protective immunity. Three signals - antigen, costimulation and inflammation - orchestrate optimal CD8+ T-cell priming and differentiation into effector and memory cells and shape T-cell functional fate and ability to protect against challenge infections. While among the conventional spleen DCs (cDCs), the CD8α+ but not the CD8α- cDCs most efficiently mediate CD8+ T-cell priming, it is unclear which subset, irrespective of their capacity to process MHC class I-associated antigens, is most efficient at inducing naïve CD8+ T-cell differentiation into pathogen-specific protective memory cells in vivo. Moreover, the origin of the required signals is still unclear. Using mice infected with the intracellular bacterium Listeria monocytogenes, we show that splenic CD8α+ cDCs become endowed with all functional features to optimally prime protective memory CD8+ T cells in vivo within only a few hours post-immunization. Such programming requires both cytosolic signals resulting from bacterial invasion of the host cells and extracellular inflammatory mediators. Thus, these data designate these cells as the best candidates to facilitate the development of cell-based vaccine therapy.
AB - Memory CD8+ T lymphocytes are critical effector cells of the adaptive immune system mediating long-lived pathogen-specific protective immunity. Three signals - antigen, costimulation and inflammation - orchestrate optimal CD8+ T-cell priming and differentiation into effector and memory cells and shape T-cell functional fate and ability to protect against challenge infections. While among the conventional spleen DCs (cDCs), the CD8α+ but not the CD8α- cDCs most efficiently mediate CD8+ T-cell priming, it is unclear which subset, irrespective of their capacity to process MHC class I-associated antigens, is most efficient at inducing naïve CD8+ T-cell differentiation into pathogen-specific protective memory cells in vivo. Moreover, the origin of the required signals is still unclear. Using mice infected with the intracellular bacterium Listeria monocytogenes, we show that splenic CD8α+ cDCs become endowed with all functional features to optimally prime protective memory CD8+ T cells in vivo within only a few hours post-immunization. Such programming requires both cytosolic signals resulting from bacterial invasion of the host cells and extracellular inflammatory mediators. Thus, these data designate these cells as the best candidates to facilitate the development of cell-based vaccine therapy.
KW - CD8a dendritic cells
KW - Listeria monocytogenes
KW - Memory CD8 T cells
KW - Protective immunity
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U2 - 10.1002/eji.201041036
DO - 10.1002/eji.201041036
M3 - Article
C2 - 21469106
AN - SCOPUS:79957541708
SN - 0014-2980
VL - 41
SP - 1594
EP - 1605
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 6
ER -