Activated NKT Cells Can Condition Different Splenic Dendritic Cell Subsets To Respond More Effectively to TLR Engagement and Enhance Cross-Priming

• Published in: The Journal of immunology (1950) 2015-08, Vol.195 (3), p.821-831
• Main Authors: Osmond, Taryn L, Farrand, Kathryn J, Painter, Gavin F, Ruedl, Christiane, Petersen, Troels R, Hermans, Ian F
• Format: Article
• Language: English
• Subjects: Animals; Antigen Presentation - immunology; Antigens, Surface - genetics; CD8-Positive T-Lymphocytes - immunology; Cross-Priming - immunology; Dendritic Cells - immunology; Interferon-alpha - biosynthesis; Interferon-alpha - immunology; Interleukin-12 - biosynthesis; Lectins, C-Type - genetics; Lymphocyte Activation - immunology; Mannose-Binding Lectins - genetics; Mice; Mice, Inbred C57BL; Mice, Transgenic; Natural Killer T-Cells - immunology; Spleen - immunology; Toll-Like Receptors - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1401751

The function of dendritic cells (DCs) can be modulated through multiple signals, including recognition of pathogen-associated molecular patterns, as well as signals provided by rapidly activated leukocytes in the local environment, such as innate-like T cells. In this article, we addressed the possibility that the roles of different murine DC subsets in cross-priming CD8(+) T cells can change with the nature and timing of activatory stimuli. We show that CD8α(+) DCs play a critical role in cross-priming CD8(+) T cell responses to circulating proteins that enter the spleen in close temporal association with ligands for TLRs and/or compounds that activate NKT cells. However, if NKT cells are activated first, then CD8α(-) DCs become conditioned to respond more vigorously to TLR ligation, and if triggered directly, these cells can also contribute to priming of CD8(+) T cell responses. In fact, the initial activation of NKT cells can condition multiple DC subsets to respond more effectively to TLR ligation, with plasmacytoid DCs making more IFN-α and both CD8α(+) and CD8α(-) DCs manufacturing more IL-12. These results suggest that different DC subsets can contribute to T cell priming if provided appropriately phased activatory stimuli, an observation that could be factored into the design of more effective vaccines.