Involvement of IL-10 in exhaustion of myeloid dendritic cells and rescue by CD40 stimulation.
It has recently been shown that immature dendritic cells (DCs) stimulated by a danger signal undergo transient maturation followed by exhaustion. However, the exact mechanism for this has not been elucidated. In this study, we show that interleukin-10 (IL-10) secreted from transiently matured DCs stimulated by danger signals is responsible for this rapid DC exhaustion. Blocking of the autocrine IL-10 enabled transient mature DCs to maintain the mature phenotype for several days. However, these DCs remained phenotypically unstable because the addition of IL-10 altered the transient mature DCs to exhausted DCs. More importantly, stimulation of DCs by CD40 protected transient mature DCs from IL-10-dependent exhaustion, with the result that mature DCs remained stable in the presence of IL-10. Furthermore, in vivo administration of stable mature DCs pulsed with ovalbumin protein induced antigen-specific cytotoxic T lymphocytes (CTLs) effectively, whereas neither exhausted DCs nor transient mature DCs were able to prime a strong antigen-specific CTL response. These results indicate that DC-T cell engagement via CD40-CD154 is required for stable DC maturation leading to effective CTL induction. Otherwise, DCs stimulated solely by a danger signal are temporarily activated, but then rapidly lose their immune-activating capacity under the influence of autocrine IL-10.
Kajino
Kiichi
K
Department of Pathology, Shiga University of Medical Science, School of Medicine, Ohtsu, Shiga 520-2192, Japan.
Nakamura
Ichiro
I
Bamba
Hiromichi
H
Sawai
Toshihiro
T
Ogasawara
Kazumasa
K
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000172:deficiency / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D019013:CD40 Antigens; D008070:Lipopolysaccharides; D016753:Interleukin-10; D010047:Ovalbumin