Tolerogenicity is not an absolute property of a dendritic cell

Claire A. Farquhar, Alison M. Paterson, Stephen P. Cobbold, Hugo Garcia Rueda, Paul J. Fairchild, Stephen F. Yates, Elizabeth Adams, Nigel J. Saunders, Herman Waldmann, Kathleen F. Nolan

    Research output: Contribution to journalArticlepeer-review


    Pharmacological modulation is known to temper the immune capacity of DC, enhancing the notion that modulated Ag-bearing DC might be used therapeutically to induce tolerance. We have investigated phenotypic features shared by such DC, and queried their potential to tolerize in different settings. Immature, IL-10, TGF-β and 1α,25-dihydroxyvitamin D3-modulated BMDC all induced tolerance to male skin in female TCR transgenic A1.RAG mice, and the modulated DC also tolerized after exposure to the TLR4-ligand LPS. Transcript profiling revealed that this was achieved despite retaining much of the normal LPS-maturation response. No shared tolerance-associated transcripts could be identified. Equivalent BMDC could not tolerize in Marilyn TCR-transgenic mice. Simultaneous presentation of both A1.RAG and Marilyn peptide-Ag (Dby-H2E k and Dby-H2Ab) on immature (C57BL/6JxCBA/Ca) F1 BMDC also only achieved tolerance in A1.RAGmice. Both strains registered Ag, but Foxp3+ Treg were only induced in A1.RAG mice. In contrast, Marilyn T cells showed greater proliferation and an inflammatory bias, in response to Ag presented by immature F1 BMDC in vitro. In summary, while pharmacological agents can skew DC to reinforce their immature tolerogenic phenotype, the outcome of presentation is ultimately an integrated response including T-cell-intrinsic components that can over-ride for immune activation. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.
    Original languageEnglish
    Pages (from-to)1728-1737
    Number of pages9
    JournalEuropean journal of immunology
    Issue number6
    Publication statusPublished - Jun 2010


    • DC
    • TCR transgenic mice
    • Transplantation tolerance


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