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Involvement of IL‐10 in exhaustion of myeloid dendritic cells and rescue by CD40 stimulation
Author(s) -
Kajino Kiichi,
Nakamura Ichiro,
Bamba Hiromichi,
Sawai Toshihiro,
Ogasawara Kazumasa
Publication year - 2007
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2006.02474.x
Subject(s) - ctl* , cd40 , autocrine signalling , cytotoxic t cell , cd154 , dendritic cell , ovalbumin , microbiology and biotechnology , immunology , stimulation , immune system , biology , receptor , neuroscience , cd8 , in vitro , biochemistry
Summary 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.