The CD8+ Dendritic Cell Subset Selectively Endocytoses Dying Cells in Culture and In Vivo

By T. Iyoda, Susumu Shimoyama, Kang Liu, Y. Omatsu, Y. Akiyama, Y. Maeda, K. Takahara, R. Steinman, K. Inaba. Journal of Experimental Medicine, 2002

707 citations recorded by the source corpus.

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.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/65035b7490cfd97e1fcf6c565e139f333f954639

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

Citations in the corpus

Immunogenic and tolerogenic cell death (2009, background): “Indeed, splenic CD8α + DCs are potent inducers of tolerance, whereas splenic CD8α − DCs promote immune response”
Characterization of human DNGR-1+ BDCA3+ leukocytes as putative equivalents of mouse CD8α+ dendritic cells (2010, background): “Human DNGR-1+ DCs internalize dead cell material and cross-present exogenous proteins to CD8+ T cells Another attribute of mouse CD8+ DCs is their superior capacity to internalize debris from dead or dying cells (Iyoda et al., 2002; Schulz and Reis e Sousa, 2002).”
Toll-like receptor 3 promotes cross-priming to virus-infected cells (2005, background): “; this in turn might be related to their ability to phagocytose dying cell”
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 (2002, background): “The DCs are active in endocytosis (40, 46) and also respond in vivo to microbial, inflammatory, and T cell stimuli by producing cytokines (47) and up-regulating several costimulatory molecules (48–50).”
Dendritic cells: translating innate to adaptive immunity. (2006, background): “mice, the CD8α+ subset of DCs is the principal cross-presenting cell in spleen and lymph nodes [5, 91, 97].”
Human CD141+ (BDCA-3)+ dendritic cells (DCs) represent a unique myeloid DC subset that cross-presents necrotic cell antigens (2010, background): “Most importantly, like human CD141+ DCs, mouse CD8+ DCs have specialized cross-presenting capacity, particularly after taking up dead/dying cells or after poly I:C activation (den Haan et al., 2000; Iyoda et al., 2002; Schulz et al., 2005; Schnorrer et al., 2006).”
Cross‐presentation, dendritic cell subsets, and the generation of immunity to cellular antigens (2004, background): “An observation of several studies is that CD8 DCs preferentially capture apoptotic cells (14, 58, 112), which they are then able to cross-present to CD8 T cells (14, 58).”
The Linkage of Innate to Adaptive Immunity via Maturing Dendritic Cells In Vivo Requires CD40 Ligation in Addition to Antigen Presentation and CD80/86 Costimulation (2004, methodology): “says described previously (7, 8) in which mice were injected with 2 10 7 OVA-pulsed and osmotically shocked, syngeneic TAP splenocytes (7).”