Cd8+ but Not Cd8− Dendritic Cells Cross-Prime Cytotoxic T Cells in Vivo

By J. D. den Haan, S. Lehar, M. Bevan. Journal of Experimental Medicine, 2000

1,476 citations recorded by the source corpus.

Bone marrow–derived antigen-presenting cells (APCs) take up cell-associated antigens and present them in the context of major histocompatibility complex (MHC) class I molecules to CD8+ T cells in a process referred to as cross-priming. Cross-priming is essential for the induction of CD8+ T cell responses directed towards antigens not expressed in professional APCs. Although in vitro experiments have shown that dendritic cells (DCs) and macrophages are capable of presenting exogenous antigens in association with MHC class I, the cross-presenting cell in vivo has not been identified. We have isolated splenic DCs after in vivo priming with ovalbumin-loaded β2-microglobulin–deficient splenocytes and show that they indeed present cell-associated antigens in the context of MHC class I molecules. This process is transporter associated with antigen presentation (TAP) dependent, suggesting an endosome to cytosol transport. To determine whether a specific subset of splenic DCs is involved in this cross-presentation, we negatively and positively selected for CD8− and CD8+ DCs. Only the CD8+, and not the CD8−, DC subset demonstrates cross-priming ability. FACS® studies after injection of splenocytes loaded with fluorescent beads showed that 1 and 0.6% of the CD8+ and the CD8− DC subsets, respectively, had one or more associated beads. These results indicate that CD8+ DCs play an important role in the generation of cytotoxic T lymphocyte responses specific for cell-associated antigens.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/c99e6dde45daa8eba92e4cea6c47f8e94260ac18

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Citations in the corpus

Steady-state and inflammatory dendritic-cell development (2007, background): “and the presentation of antigens on MHC class I molecule”
Cross‐presentation, dendritic cell subsets, and the generation of immunity to cellular antigens (2004, background): “Perhaps, the most important property of CD8 DCs with respect to this review is their central role in cross-priming (11) and cross-tolerance (64, 111), which is examined in more detail in the next section.”
The CD8+ Dendritic Cell Subset Selectively Endocytoses Dying Cells in Culture and In Vivo (2002, background): “It has been reported that CD8 DCs in vivo selectively cross present OVA to OT-I T cells (19).”
Notch–RBP-J signaling controls the homeostasis of CD8− dendritic cells in the spleen (2007, background): “This DC subset is uniquely capable of the cross-presentation of cell-associated antigens via the MHC class I pathway (3, 6).”
Dendritic-cell immunotherapy: from ex vivo loading to in vivo targeting (2007, result): “Mouse splenic CD8 + DCs were shown to cross-present antigen to T cells in vitro , in contrast to CD8 − DC”
Dynamics and function of Langerhans cells in vivo: dermal dendritic cells colonize lymph node areas distinct from slower migrating Langerhans cells. (2005, methodology): “After gating out autofluorescent cells (mostly macrophages) by using the FL3 or FL6 channel (den Haan et al., 2000; Wilson et al., 2003), large cells (as defined using FSC versus SSC profile) were analyzed for expression of EGFP and CD11c.”
Mouse and human dendritic cell subtypes (2002, background): “Many experiments now point to DCs being the previously elusive cross-presenting APC”
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).”