Plasmacytoid DCs regulate recall responses by rapid induction of IL-10 in memory T cells.
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.
Kvale
Espen O
EO
Laboratory for Immunohistochemistry and Immunopathology, Institute of Pathology, University of Oslo, Rikshospitalet-Radiumhospitalet Medical Center, N-0027 Oslo, Norway. e.o.kvale@medisin.uio.no
Fløisand
Yngvar
Y
Lund-Johansen
Fridtjof
F
Rollag
Halvor
H
Farkas
Lorant
L
Ghanekar
Smita
S
Brandtzaeg
Per
P
Jahnsen
Frode L
FL
Olweus
Johanna
J
D000956:Antigens, Viral / Q000276:immunology / Q000494:pharmacology; D024201:Bystander Effect / Q000187:drug effects / Q000276:immunology; D039521:CD11c Antigen / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D004768:Enterotoxins / Q000276:immunology / Q000494:pharmacology; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects; D007370:Interferon Type I / Q000276:immunology / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology* / Q000378:metabolism; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism
D000956:Antigens, Viral; D039521:CD11c Antigen; D004768:Enterotoxins; C508609:IL10 protein, human; D007370:Interferon Type I; D016753:Interleukin-10; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma