title: Human blood CD1c dendritic cells stimulate IL-12-independent IFN-γresponses and have a strikingly low inflammatory profile.
abstract: Adaptive immune responses are initiated by resident myeloid tissue DC. A major fraction of tissue DC express CD1c+and is thought to be derived from blood CD1c DC, an idea supported here by the observation that they express tissue-homing molecules and rapidly differentiate into cells with a tissue DC phenotype. Responses are thought to be augmented/modulated further by inflammatory moDC. Although much accepted human myeloid DC cell biology is based on moDC studies, we find these 2 DC populations to be functionally distinct. Stimulated moDC produce high levels of IL-10 and the Th1-promoting cytokine IL-12. Under identical conditions, CD1c DC synthesized no IL-10 and no or low levels of IL-12. Despite this, CD1c DC stimulated a strong Th1 response, demonstrated by IL-12 neutralization to be IL-12 independent, whereas the response induced by moDC was IL-12 dependent. This finding was supported by studies on a patient with a highly reduced ability to synthesize IL-12, whose CD1c DC induced a good Th1 response contrasting with the failure of his moDC, which were impaired in IL-12 production, to induce IFN-γ-secreting T cells. The IL-10 and IL-12 data were confirmed by microarray analysis, which also showed that stimulated moDC produced inflammatory-associated chemokines and cytokines, whereas stimulated CD1c DC showed minimal up-regulation of these genes. Thus, moDC, widely used as a human myeloid DC model, do not faithfully reflect the properties of CD1c tissue DC, making the initial response to a pathogen or vaccine.
authors.affiliation: *Centre for Immunology and Vaccinology, Imperial College London, Chelsea and Westminster Hospital, London, United Kingdom; University College London Genomics/Division of Infection and Immunity, University College London, London, United Kingdom; Department of Cellular and Cytokine Biology, Kennedy Institute of Rheumatology, Imperial College, London, United Kingdom; and Infection and Immunity Laboratory, Charing Cross Hospital, Imperial College Healthcare National Health Service Trust, London, United Kingdom.
authors.forename: Adel
authors.initials: A
authors.lastname: Benlahrech
authors.affiliation: *Centre for Immunology and Vaccinology, Imperial College London, Chelsea and Westminster Hospital, London, United Kingdom; University College London Genomics/Division of Infection and Immunity, University College London, London, United Kingdom; Department of Cellular and Cytokine Biology, Kennedy Institute of Rheumatology, Imperial College, London, United Kingdom; and Infection and Immunity Laboratory, Charing Cross Hospital, Imperial College Healthcare National Health Service Trust, London, United Kingdom.
authors.forename: Sai
authors.initials: S
authors.lastname: Duraisingham
authors.affiliation: *Centre for Immunology and Vaccinology, Imperial College London, Chelsea and Westminster Hospital, London, United Kingdom; University College London Genomics/Division of Infection and Immunity, University College London, London, United Kingdom; Department of Cellular and Cytokine Biology, Kennedy Institute of Rheumatology, Imperial College, London, United Kingdom; and Infection and Immunity Laboratory, Charing Cross Hospital, Imperial College Healthcare National Health Service Trust, London, United Kingdom.
authors.forename: Douglas
authors.initials: D
authors.lastname: King
authors.affiliation: *Centre for Immunology and Vaccinology, Imperial College London, Chelsea and Westminster Hospital, London, United Kingdom; University College London Genomics/Division of Infection and Immunity, University College London, London, United Kingdom; Department of Cellular and Cytokine Biology, Kennedy Institute of Rheumatology, Imperial College, London, United Kingdom; and Infection and Immunity Laboratory, Charing Cross Hospital, Imperial College Healthcare National Health Service Trust, London, United Kingdom.
authors.forename: Lisa
authors.initials: L
authors.lastname: Verhagen
authors.affiliation: *Centre for Immunology and Vaccinology, Imperial College London, Chelsea and Westminster Hospital, London, United Kingdom; University College London Genomics/Division of Infection and Immunity, University College London, London, United Kingdom; Department of Cellular and Cytokine Biology, Kennedy Institute of Rheumatology, Imperial College, London, United Kingdom; and Infection and Immunity Laboratory, Charing Cross Hospital, Imperial College Healthcare National Health Service Trust, London, United Kingdom.
authors.forename: George
authors.initials: G
authors.lastname: Rozis
authors.affiliation: *Centre for Immunology and Vaccinology, Imperial College London, Chelsea and Westminster Hospital, London, United Kingdom; University College London Genomics/Division of Infection and Immunity, University College London, London, United Kingdom; Department of Cellular and Cytokine Biology, Kennedy Institute of Rheumatology, Imperial College, London, United Kingdom; and Infection and Immunity Laboratory, Charing Cross Hospital, Imperial College Healthcare National Health Service Trust, London, United Kingdom.
authors.forename: Parisa
authors.initials: P
authors.lastname: Amjadi
authors.affiliation: *Centre for Immunology and Vaccinology, Imperial College London, Chelsea and Westminster Hospital, London, United Kingdom; University College London Genomics/Division of Infection and Immunity, University College London, London, United Kingdom; Department of Cellular and Cytokine Biology, Kennedy Institute of Rheumatology, Imperial College, London, United Kingdom; and Infection and Immunity Laboratory, Charing Cross Hospital, Imperial College Healthcare National Health Service Trust, London, United Kingdom.
authors.forename: Tom
authors.initials: T
authors.lastname: Ford
authors.affiliation: *Centre for Immunology and Vaccinology, Imperial College London, Chelsea and Westminster Hospital, London, United Kingdom; University College London Genomics/Division of Infection and Immunity, University College London, London, United Kingdom; Department of Cellular and Cytokine Biology, Kennedy Institute of Rheumatology, Imperial College, London, United Kingdom; and Infection and Immunity Laboratory, Charing Cross Hospital, Imperial College Healthcare National Health Service Trust, London, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Kelleher
authors.affiliation: *Centre for Immunology and Vaccinology, Imperial College London, Chelsea and Westminster Hospital, London, United Kingdom; University College London Genomics/Division of Infection and Immunity, University College London, London, United Kingdom; Department of Cellular and Cytokine Biology, Kennedy Institute of Rheumatology, Imperial College, London, United Kingdom; and Infection and Immunity Laboratory, Charing Cross Hospital, Imperial College Healthcare National Health Service Trust, London, United Kingdom s.patterson@imperial.ac.uk.
authors.forename: Steven
authors.initials: S
authors.lastname: Patterson
keywords: Th1; cytokines; microarray; monocyte