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Blood, 15 April 2007, Vol. 109, No. 8, pp. 3369-3376.
Prepublished online as a Blood First Edition Paper on December 7, 2006; DOI 10.1182/blood-2006-06-031484.


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IMMUNOBIOLOGY

Plasmacytoid DCs regulate recall responses by rapid induction of IL-10 in memory T cells

Espen O. Kvale1,2, Yngvar Fløisand2, Fridtjof Lund-Johansen2,3, Halvor Rollag4, Lorant Farkas1, Smita Ghanekar5, Per Brandtzaeg1, Frode L. Jahnsen1, and Johanna Olweus2

1 Laboratory for Immunohistochemistry and Immunopathology, Institute of Pathology, University of Oslo, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway; 2 Institute of Immunology, Rikshospitalet-Radiumhospitalet Medical Center, University of Oslo, Norway; 3 Section of Hematology, Department of Medicine, University of Oslo, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway; 4 Institute of Medical Microbiology, University of Oslo, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway; 5 BD Biosciences, San Jose, CA

Dendritic cells (DCs) are believed to regulate T cell-mediated immunity primarily by directing differentiation of naive T cells. Here, we show that a large fraction of CD4+ memory cells produce IL-10 within the first hours after interaction with plasmacytoid DCs (PDCs). In contrast, CD11c+ DCs induce IFN-{gamma} and little IL-10. IL-10–secreting T cells isolated after 36 hours of culture with PDCs suppressed antigen-induced T-cell proliferation by an IL-10–dependent mechanism, but were distinct from natural and type 1 regulatory T cells. They proliferated strongly and continued to secrete IL-10 during expansion with PDCs, and after restimulation with immature monocyte-derived DCs or CD11c+ DCs. The IL-10–producing T cells acquired the ability to secrete high levels of IFN-{gamma} after isolation and subsequent coculture with PDCs or CD11c+ DCs. Compared to CD11c+ DCs, PDCs were superior in their ability to selectively expand T cells that produced cytokines on repeated antigenic challenge. The DC-dependent differences in cytokine profiles were observed with viral recall antigen or staphylococcal enterotoxin B and were independent of extracellular type I interferon or IL-10. Our results show that DCs can regulate memory responses and that PDCs rapidly induce regulatory cytokines in effector T cells that can suppress bystander activity.


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