Splenic CD8[alpha] super(+) dendritic cells undergo rapid programming by cytosolic bacteria and inflammation to induce protective CD8 super(+) T-cell memory

• Published in: European journal of immunology 2011-06, Vol.41 (6), p.1594-1605
• Main Authors: Campisi, Laura, Soudja, Saidi M'Homa, Cazareth, Julie, Bassand, Delphine, Lazzari, Anne, Brau, Frederic, Narni-Mancinelli, Emilie, Glaichenhaus, Nicolas, Geissmann, Frederic, Lauvau, Gregoire
• Format: Article
• Language: English
• Subjects: Listeria monocytogenes
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201041036

Memory CD8 super(+) 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 super(+) 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 CD8[alpha] super(+) but not the CD8[alpha] super(-) cDCs most efficiently mediate CD8 super(+) T-cell priming, it is unclear which subset, irrespective of their capacity to process MHC class I-associated antigens, is most efficient at inducing naive CD8 super(+) 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 CD8[alpha] super(+) cDCs become endowed with all functional features to optimally prime protective memory CD8 super(+) 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.