Cutting edge: Generation of splenic CD8+ and CD8- dendritic cell equivalents in Fms-like tyrosine kinase 3 ligand bone marrow cultures

Shalin H. Naik, Anna I Proietto, Nicholas S. Wilson, Aleksandar Dakic, Petra Schnorrer, Martina Fuchsberger, Mireille H. Lahoud, Meredith O'Keeffe, Qi Xiang Shao, Wei Feng Chen, José A. Villadangos, Ken Shortman, Li Wu

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370 Citations (Scopus)

Abstract

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 bonafide counterparts of the splenic DC subsets.

Original languageEnglish
Pages (from-to)6592-6597
Number of pages6
JournalJournal of Immunology
Volume174
Issue number11
Publication statusPublished - 1 Jun 2005
Externally publishedYes

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