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Timing and intensity of exposure to interferon‐ γ critically determines the function of monocyte‐derived dendritic cells
Author(s) -
Kerkar Sid P.,
Chinnasamy Dhanalakshmi,
Hadi Neima,
Melenhorst Jan,
Muranski Pawel,
Spyridonidis Alexandros,
Ito Sawa,
Weber Gerrit,
Yin Fang,
Hensel Nancy,
Wang Ena,
Marincola Francesco M.,
Barrett Austin John
Publication year - 2014
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/imm.12292
Subject(s) - monocyte , dendritic cell , immunology , biology , antigen , antigen presentation , interferon , lipopolysaccharide , microbiology and biotechnology , immune system , mhc class ii , t cell , cellular differentiation , antigen presenting cell , gene , biochemistry
Summary A growing body of evidence suggests that inflammatory cytokines have a dualistic role in immunity. In this study, we sought to determine the direct effects of interferon‐ γ ( IFN ‐ γ ) on the differentiation and maturation of human peripheral blood monocyte‐derived dendritic cells (mo DC ). Here, we report that following differentiation of monocytes into mo DC with granulocyte–macrophage colony‐stimulating factor and interleukin‐4, IFN ‐ γ induces mo DC maturation and up‐regulates the co‐stimulatory markers CD 80/ CD 86/ CD 95 and MHC Class I, enabling mo DC to effectively generate antigen‐specific CD 4 + and CD 8 + T‐cell responses for multiple viral and tumour antigens. Early exposure of monocytes to high concentrations of IFN ‐ γ during differentiation promotes the formation of macrophages. However, under low concentrations of IFN ‐ γ , monocytes continue to differentiate into dendritic cells possessing a unique gene‐expression profile, resulting in impairments in subsequent maturation by IFN ‐ γ or lipopolysaccharide and an inability to generate effective antigen‐specific CD 4 + and CD 8 + T‐cell responses. These findings demonstrate that IFN ‐ γ imparts differential programmes on mo DC that shape the antigen‐specific T‐cell responses they induce. Timing and intensity of exposure to IFN ‐ γ can therefore determine the functional capacity of mo DC .