Timing and intensity of exposure to interferon‐γ critically determines the function of monocyte‐derived dendritic cells. Issue 1 (September 2014)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Immunology. Volume 143:Issue 1(2014:Sep.)
• Page Start: 96
• Page End: 108
• Publication Date: 2014-09
• Subjects: Immunology -- Periodicals
• DOI: 10.1111/imm.12292
• Languages: English
• ISSNs: 0019-2805

Abstract

<abstract abstract-type="main" id="imm12292-abs-0001"> <title>Summary</title> <p>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‐<italic>γ</italic> (IFN‐<italic>γ</italic>) on the differentiation and maturation of human peripheral blood monocyte‐derived dendritic cells (moDC). Here, we report that following differentiation of monocytes into moDC with granulocyte–macrophage colony‐stimulating factor and interleukin‐4, IFN‐<italic>γ</italic> induces moDC maturation and up‐regulates the co‐stimulatory markers CD80/CD86/CD95 and MHC Class I, enabling moDC to effectively generate antigen‐specific CD4<sup>+</sup> and CD8<sup>+</sup> T‐cell responses for multiple viral and tumour antigens. Early exposure of monocytes to high concentrations of IFN‐<italic>γ</italic> during differentiation promotes the formation of macrophages. However, under low concentrations of IFN‐<italic>γ</italic>, monocytes continue to differentiate into dendritic cells possessing a unique gene‐expression profile, resulting in impairments in subsequent maturation by IFN‐<italic>γ</italic> or lipopolysaccharide and an inability to generate effective antigen‐specific CD4<sup>+</sup> and CD8<sup>+</sup> T‐cell responses. These findings demonstrate that IFN‐<italic>γ</italic> imparts differential programmes on moDC that shape the antigen‐specific T‐cell responses they induce. Timing and intensity of exposure to IFN‐<italic>γ</italic> can therefore determine the functional capacity of moDC.</p> </abstract>