The CD8+ Dendritic Cell Subset Selectively Endocytoses Dying Cells in Culture and In Vivo
Tomonori Iyoda,Susumu Shimoyama,Kang Liu,Yoshiki Omatsu,Yuji Akiyama,Yasuhiro Maeda,Kazuhiko Takahara,Ralph M. Steinman,Kayo Inaba +8 more
TLDR
It is shown directly that DCs in situ take up these types of cells after fluorescent labeling with carboxyfluorescein succinimidyl ester and injection into mice, indicating their selective ability to cross present cellular antigens to both CD4+ and CD8+ T cells.Abstract:
Dendritic cells (DCs) are able in tissue culture to phagocytose and present antigens derived from infected, malignant, and allogeneic cells. Here we show directly that DCs in situ take up these types of cells after fluorescent labeling with carboxyfluorescein succinimidyl ester (CFSE) and injection into mice. The injected cells include syngeneic splenocytes and tumor cell lines, induced to undergo apoptosis ex vivo by exposure to osmotic shock, and allogeneic B cells killed by NK cells in situ. The CFSE-labeled cells in each case are actively endocytosed by DCs in vivo, but only the CD8+ subset. After uptake, all of the phagocytic CD8+ DCs can form major histocompatibility complex class II–peptide complexes, as detected with a monoclonal antibody specific for these complexes. The CD8+ DCs also selectively present cell-associated antigens to both CD4+ and CD8+ T cells. Similar events take place with cultured DCs; CD8+ DCs again selectively take up and present dying cells. In contrast, both CD8+ and CD8− DCs phagocytose latex particles in culture, and both DC subsets present soluble ovalbumin captured in vivo. Therefore CD8+ DCs are specialized to capture dying cells, and this helps to explain their selective ability to cross present cellular antigens to both CD4+ and CD8+ T cells.read more
Citations
More filters
Journal ArticleDOI
Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA.
TL;DR: These results identify ssRNA as a ligand for TLR7 and suggest that cells of the innate immune system sense endosomal ssRNA to detect infection by RNA viruses.
Journal ArticleDOI
Tolerogenic dendritic cells.
TL;DR: It is suggested that several clinical situations, including autoimmunity and certain infectious diseases, can be influenced by the antigen-specific tolerogenic role of DCs.
Journal ArticleDOI
Taking dendritic cells into medicine
TL;DR: Some medical implications of DC biology that account for illness and provide opportunities for prevention and therapy are presented.
Journal ArticleDOI
The dendritic cell lineage: ontogeny and function of dendritic cells and their subsets in the steady state and the inflamed setting.
TL;DR: This review discusses major advances in the understanding of the regulation of DC lineage commitment, differentiation, diversification, and function in situ.
Journal ArticleDOI
Efficient Targeting of Protein Antigen to the Dendritic Cell Receptor DEC-205 in the Steady State Leads to Antigen Presentation on Major Histocompatibility Complex Class I Products and Peripheral CD8+ T Cell Tolerance
Laura Bonifaz,David P. Bonnyay,Karsten Mahnke,Karsten Mahnke,Miguel Rivera,Michel C. Nussenzweig,Michel C. Nussenzweig,Ralph M. Steinman +7 more
TL;DR: DEC-205 provides an efficient receptor-based mechanism for dendritic cells to process proteins for MHC class I presentation in vivo, leading to tolerance in the steady state and immunity after DC maturation.
References
More filters
Journal ArticleDOI
Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor.
K Inaba,M Inaba,Nikolaus Romani,H Aya,Masashi Deguchi,Susumu Ikehara,Shigeru Muramatsu,Ralph M. Steinman +7 more
TL;DR: The methodology for inducing dendritic cell growth that was recently described for mouse blood now has been modified to MHC class II- negative precursors in marrow, and this feature should prove useful for future molecular and clinical studies of this otherwise trace cell type.
Journal ArticleDOI
In search of the 'missing self': MHC molecules and NK cell recognition.
Hans-Gustaf Ljunggren,Klas Kärre +1 more
TL;DR: In vivo studies with H-2-deficient targets that support the 'missing self' hypothesis are reviewed and testable predictions for how MHC class I molecules act in cases where they control a rate-limiting step in the NK cell-target interaction are derived.
Journal ArticleDOI
Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs
TL;DR: It is shown that human dendritic cells, but not macrophages, efficiently present antigen derived from apoptotic cells, stimulating class I-restricted CD8+ CTLs, suggesting a mechanism by which potent APCs acquire antigens from tumours, transplants, infected cells, or even self-tissue, for stimulation or tolerization of C TLs.
Journal ArticleDOI
Subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens.
Norimitsu Kadowaki,Stephen Ho,Svetlana Antonenko,Rene de Waal Malefyt,Robert A. Kastelein,J. Fernando Bazan,Yong-Jun Liu +6 more
TL;DR: The expression of distinct sets of TLRs and the corresponding difference in reactivity to microbial molecules among subsets of pre-DCs and imDCs support the concept that they have developed through distinct evolutionary pathways to recognize different microbial antigens.
Journal ArticleDOI
Dendritic Cells Induce Peripheral T Cell Unresponsiveness under Steady State Conditions in Vivo
Daniel Hawiger,Kayo Inaba,Kayo Inaba,Yair Dorsett,Ming Guo,Karsten Mahnke,Miguel Rivera,Jeffrey V. Ravetch,Ralph M. Steinman,Michel C. Nussenzweig,Michel C. Nussenzweig +10 more
TL;DR: An antigen delivery system targeting these specialized antigen presenting cells in vivo using a monoclonal antibody to a DC-restricted endocytic receptor is devised, which concludes that in the absence of additional stimuli DCs induce transient antigen-specific T cell activation followed by T cell deletion and unresponsiveness.