In this present study, we characterise the global transcriptional signatures at this time point in ovine afferent lymph cells as they migrate from the injection site into the lymphatics following vaccination with a liposome antigen formulation incorporating CpG. We show that at 72h post vaccination,

liposomes alone Doxorubicin cost induce no changes in gene expression and inflammatory profiles within afferent lymph; however the incorporation of CpG drives interferon, antiviral and cytotoxic gene programs. This study also measures the expression of key genes within individual cell types in afferent lymph. Antiviral gene signatures are most prominent in lymphocytes, which may play a significant and unexpected role in sustaining the immune response to vaccination at the site of injection. These findings provide a comprehensive analysis of the in vivo immunological pathways that connect the injection site with the local draining lymph node following vaccination.

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“IFN-α/β link innate and adaptive immune responses by directly acting on naïve CD8+ T cells. This concept unveiled in mice remains unexplored in humans. To investigate that, human CD8+CD45RO− cells were stimulated with beads coated with anti-CD3 and anti-CD28 mAb, mimicking Ag (type-1) and Pirfenidone co-stimulatory (type-2) signals, in the presence or absence of IFN-α and their transcriptional profiles were defined by cDNA-microarrays. We show that IFN-α provides a strong third signal directly to human CD8+ T cells resulting in regulation of critical genes for their overall activation. This transcriptional effect was substantiated

at the protein level and verified by functional assays. Interestingly, the biological effects derived from new this stimulation vary depending on the CD8+ T-cell population. Thus, whereas IFN-α increases the proliferative capacity of naïve CD8+ T cells, it inhibits or does not affect the proliferation of Ag-experienced cells, such as memory and effector CTL, including CMV-specific lymphocytes. Cytolysis and IFN-γ-secretion of all these populations are enhanced by IFN-α-derived signals, which are critical in naïve CD8+ T cells for acquisition of effector functions. Our findings in human CD8+ T cells are informative to understand and improve IFN-α-based therapies for viral and malignant diseases. Type I IFN (IFN-I) comprises a cytokine family that in humans includes 13 IFN-α subtypes and single proteins for IFN-β, IFN-ε, IFN-κ and IFN-ω 1. IFN-α/β are produced in response to viruses and are critical for viral defense. IFN-I signals through a common receptor (IFNAR) composed of two subunits, IFNAR1 and IFNAR2 2. The JAK-STAT pathway is critical for IFNAR signaling 3.