Abstract
Cross-presentation of cell-associated antigens (Ag) plays an important role in the induction of anti-tumor responses, autoimmune diseases, and transplant rejection. While several dendritic cell (DC) populations can induce pro-inflammatory CD8+ T cell responses to cell-associated Ag during infection, in the absence of infection, cross-priming of naïve CD8+ T cells is highly restricted. Comparison of the main splenic DC populations in mice – including the classic, cross-presenting CD8α DC and the recently described merocytic DC (mcDC) – reveals that cross-priming DCs display a distinct phenotype in cell-associated Ag uptake, endosomal/lysosomal trafficking, lysosomal acidification, and Ag persistence compared to non-cross-priming DC populations. Although the CD8α DC and mcDC subsets utilize similar processing pathways to cross-present cell-associated Ag, cross-priming by CD8α DCs is associated with IL-12 production, while the superior priming of the mcDC is critically dependent on type I IFN production. This discussion illustrates how subtle differences in internal processing pathways and their signaling sequelae significantly affect the duration of Ag cross-presentation and cytokine production by DCs, thereby shaping the ensuing CD8+ T cell response.
Highlights
Every day millions of cells die in the human body, producing cellular corpses and material that must be disposed of
Comparison of the main splenic dendritic cell (DC) populations in mice – including the classic, cross-presenting CD8α DC and the recently described merocytic DC – reveals that cross-priming DCs display a distinct phenotype in cell-associated Ag uptake, endosomal/lysosomal trafficking, lysosomal acidification, and Ag persistence compared to non-cross-priming DC populations
The CD8α DC and merocytic DC (mcDC) subsets utilize similar processing pathways to cross-present cell-associated Ag, cross-priming by CD8α DCs is associated with IL-12 production, while the superior priming of the mcDC is critically dependent on type I IFN production
Summary
Every day millions of cells die in the human body, producing cellular corpses and material that must be disposed of. Cells treated with irradiation or chemotherapy become apoptotic but tend to be immunogenic (Ronchetti et al, 1999; Janssen et al, 2006; Green et al, 2009; Reboulet et al, 2010; Ferguson et al, 2011) In this context immunity probably results from the irradiation or chemical induced release of damage associated molecular proteins (DAMPS) such as high mobility group box 1 (HMGB1), uric acid/mono-sodium urate crystals, heat shock proteins, and nucleotide structures from the dying cell (Green et al, 2009; Poon et al, 2010). Seminal work over the last decade addressing uptake and processing of cell-associated Ag by phagocytes has elucidated common www.frontiersin.org
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
