Submitted June 26, 2006
Accepted November 30, 2006
Plasmacytoid DCs regulate recall responses by rapid induction of IL-10 in memory T cells
Espen O Kvale*, Yngvar Floisand, Fridtjof Lund-Johansen, Halvor Rollag, Lorant Farkas, Smita Ghanekar, Per Brandtzaeg, Frode L Jahnsen, and Johanna Olweus
Laboratory for Immunohistochemistry and Immunopathology, Institute of Pathology, University of Oslo, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway
Institute of Immunology, University of Oslo, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway
Section of Hematology, Department of Medicine, University of Oslo, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway
Institute of Medical Microbiology, University of Oslo, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway
BD Biosciences, San Jose, CA, United States
* Corresponding author; email: e.o.kvale{at}medisin.uio.no.
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-
and little IL-10. IL-10-secreting T cells isolated after 36 h 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 re-stimulation with immature monocyte-derived DCs or CD11c+ DCs. The IL-10-producing T cells acquired the ability to secrete high levels of IFN- after isolation and subsequent co-culture with PDCs or CD11c+ DCs. Compared to CD11c+ DCs, PDCs were superior in their ability to selectively expand T cells that produced cytokines upon 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.
