Cutting Edge: Generation of Splenic CD8+ and CD8− Dendritic Cell Equivalents in Fms-Like Tyrosine Kinase 3 Ligand Bone Marrow Cultures1

By Shalin H. Naik, Anna I. Proietto, N. Wilson, Aleksandar Dakic, P. Schnorrer, M. Fuchsberger, M. Lahoud, Meredith O'Keeffe, Qi-Xiang Shao, Weifeng Chen and 3 more. Journal of Immunology, 2005

602 citations recorded by the source corpus.

We demonstrate that functional and phenotypic equivalents of mouse splenic CD8+ and CD8− conventional dendritic cell (cDC) subsets can be generated in vitro when bone marrow is cultured with fms-like tyrosine kinase 3 (flt3) ligand. In addition to CD45RAhigh plasmacytoid DC, two distinct CD24high and CD11bhigh cDC subsets were present, and these subsets showed equivalent properties to splenic CD8+ and CD8− cDC, respectively, in the following: 1) surface expression of CD11b, CD24, and signal regulatory protein-α; 2) developmental dependence on, and mRNA expression of, IFN regulatory factor-8; 3) mRNA expression of TLRs and chemokine receptors; 4) production of IL-12 p40/70, IFN-α, MIP-1α, and RANTES in response to TLR ligands; 5) expression of cystatin C; and 6) cross-presentation of exogenous Ag to CD8 T cells. Furthermore, despite lacking surface CD8 expression, the CD24high subset contained CD8 mRNA and up-regulated surface expression when transferred into mice. This culture system allows access to bona fide counterparts of the splenic DC subsets.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/fefdee94a05891e9c9b9cb8692d326909461681c

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In Immunology

1. Shizuo Akira
2. H. Hammad
3. B. Lambrecht
4. R. Steinman
5. C. Reis e Sousa
6. J. Tschopp
7. O. Joffre
8. M. Willart

Citations in the corpus

• Microbial stimulation fully differentiates monocytes to DC-SIGN/CD209+ dendritic cells for immune T cell areas (2010, methodology): “To compare Mo-DCs with classical DCs that had also been derived from marrow cultures, we used a Flt3-L culture system as described by Naik et al. (2005) (Figure S1E).”
• Quantitative proteomics reveals subset-specific viral recognition in dendritic cells. (2010, methodology): “…(FL) to generate FLDCs containing phenotypic and functional equivalents of CD8a+ cDCs (eCD8+) and equivalents of both CD4+ and DN cDCs (eCD8 ) (Naik et al., 2005) were also prepared from WT, Myd88 / , and Mavs / mice. eCD8 DCs, but not eCD8+ DCs of WT and Myd88 / mice, were still able to…”
• Inflammatory dendritic cells—not basophils—are necessary and sufficient for induction of Th2 immunity to inhaled house dust mite allergen (2010, background): “When Flt3L cultures were studied more carefully, FcRI expression was not detected on CD24+ (CD8+ equivalent) cDCs, CD24 cDCs (CD8 equivalent), or 120G8+ pDCs (Naik et al., 2005).”
• Characterization of human DNGR-1+ BDCA3+ leukocytes as putative equivalents of mouse CD8α+ dendritic cells (2010, background): “The expanded cells were then aliquoted and tested in a variety of differentiation conditions for the ability to generate DNGR-1+ and/or BDCA3+ DCs. Flt3L was included in the differentiation “cocktail” because BDCA3+ DCs are expanded in Flt3L-treated human subjects (Galibert et al., 2005), and Flt3L ”
• The XC chemokine receptor 1 is a conserved selective marker of mammalian cells homologous to mouse CD8α+ dendritic cells (2010, background): “3 A), which correspond to a subset of in vitro–derived DCs equivalent to spleen CD8+ DCs which can be referred to as eCD8+ DCs (Naik et al., 2005).”