Activation of influenza virus-specific CD4+ and CD8+ T cells: a new role for plasmacytoid dendritic cells in adaptive immunity.
Plasmacytoid dendritic cells (pDCs) contribute to innate antiviral immune responses by producing type I interferons (IFNs) upon exposure to enveloped viruses. However, their role in adaptive immune responses, such as the initiation of antiviral T-cell responses, is not known. In this study, we examined interactions between blood pDCs and influenza virus with special attention to the capacity of pDCs to activate influenza-specific T cells. pDCs were compared with CD11c(+) DCs, the most potent antigen-presenting cells (APCs), for their capacity to activate T-cell responses. We found that like CD11c(+) DCs, pDCs mature following exposure to influenza virus, express CCR7, and produce proinflammatory chemokines, but differ in that they produce type I IFN and are resistant to the cytopathic effect of the infection. After influenza virus exposure, both DC types exhibited an equivalent efficiency to expand anti-influenza virus cytotoxic T lymphocytes (CTLs) and T helper 1 (TH1) CD4(+) T cells. Our results pinpoint a new role of pDCs in the induction of antiviral T-cell responses and suggest that these DCs play a prominent role in the adaptive immune response against viruses.
Fonteneau
Jean-François
JF
Laboratory of Molecular Neuro-Oncology, Rockefeller University, New York, NY, USA.
Gilliet
Michel
M
Larsson
Marie
M
Dasilva
Ida
I
Münz
Christian
C
Liu
Yong-Jun
YJ
Bhardwaj
Nina
N
D017951:Antigen Presentation; D000956:Antigens, Viral / Q000276:immunology* / Q000502:physiology; D039521:CD11c Antigen / Q000032:analysis; D002478:Cells, Cultured / Q000276:immunology / Q000378:metabolism; D018925:Chemokines / Q000096:biosynthesis; D003588:Cytopathogenic Effect, Viral; D003713:Dendritic Cells / Q000145:classification / Q000276:immunology* / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology*; D016898:Interferon-alpha / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000096:biosynthesis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000276:immunology*
D000956:Antigens, Viral; C515370:CCR7 protein, human; D039521:CD11c Antigen; D018925:Chemokines; D015789:HLA-A2 Antigen; D016898:Interferon-alpha; D010446:Peptide Fragments; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D014763:Viral Matrix Proteins; C098952:influenza virus membrane protein (58-66)