Anti-CD1C monoclonal antibody, clone 3E5

Strong innate and adaptive immune responses are paramount in combating viral infections. Dendritic cells (DCs) detect viral infections via cytosolic RIG-I like receptors (RLRs) RIG-I and MDA5 leading to MAVS-induced immunity. The DEAD-box RNA helicase DDX3 senses abortive human immunodeficiency virus 1 (HIV-1) transcripts and induces MAVS-dependent type I interferon (IFN) responses, suggesting that abortive HIV-1 RNA transcripts induce antiviral immunity. Little is known about the induction of antiviral immunity by DDX3-ligand abortive HIV-1 RNA. Here we synthesized a 58 nucleotide-long capped RNA (HIV-1 Cap-RNA(58)) that mimics abortive HIV-1 RNA transcripts. HIV-1 Cap-RNA(58) induced potent type I IFN responses in monocyte-derived DCs, monocytes, macrophages and primary CD1c(+) DCs. Compared with RLR agonist poly-I:C, HIV-1 Cap-RNA(58) induced comparable levels of type I IFN responses, identifying HIV-1 Cap-RNA(58) as a potent trigger of antiviral immunity. In monocyte-derived DCs, HIV-1 Cap-RNA(58) activated the transcription factors IRF3 and NF-kappa B. Moreover, HIV-1 Cap-RNA(58) induced DC maturation and the expression of pro-inflammatory cytokines. HIV-1 Cap-RNA(58)-stimulated DCs induced proliferation of CD4(+) and CD8(+) T cells and differentiated naive T helper (T-H) cells toward a T(H)2 phenotype. Importantly, treatment of DCs with HIV-1 Cap-RNA(58) resulted in an efficient antiviral innate immune response that reduced ongoing HIV-1 replication in DCs. Our data strongly suggest that HIV-1 Cap-RNA(58) induces potent innate and adaptive immune responses, making it an interesting addition in vaccine design strategies.

PURPOSE. Myeloid dendritic cells (mDCs) play an important role in autoimmune diseases. However, the role of blood CD1c(+) myeloid dendritic cells 1 (mDC1s), the subset of human blood mDCs, is not well understood in noninfectious uveitis. METHODS. Fresh peripheral blood samples from human noninfectious uveitis patients (n = 32) and healthy controls (HCs) (n = 64) were stained with FITC-Lineage 1 (Lin1), PERCP-HLADR, and PE-CD1c antibodies. The levels of mDC1 were quantified by using flow cytometric analysis. Longitudinal data from patients (n = 16) were analyzed to correlate the levels of mDC1 with disease activity. RESULTS. Blood CD1c(+) mDC1 and its subpopulation, CD1c(hi) mDC1, were increased in uveitis patients compared with HCs. Longitudinal data demonstrated that both the CD1c(+) mDC1 and CD1c(hi) mDC1 subpopulation reflected a dynamic change in clinical uveitis activity: CD1c expression was increased in active uveitis but decreased when uveitis became inactive. CONCLUSIONS. Given these observations, an alteration in blood CD1c(+) mDC1 and the CD1c(hi) mDC1 subpopulation could be a potential biomarker to monitor clinical uveitis activity within patients.