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Lymph node (LN) fine needle aspiration (LN FNA) represents a powerful technique for minimally invasive sampling of human LNs in vivo and has been used effectively to directly study aspects of the human germinal center response. However, systematic deep phenotyping of the cellular populations and cell‐free proteins recovered by LN FNA has not been performed. Thus, we studied human cervical LN FNAs as a proof‐of‐concept and used single‐cell RNA‐sequencing and proteomic analysis to benchmark this compartment, define the purity of LN FNA material, and facilitate future studies in this immunologically pivotal environment. Our data provide evidence that LN FNAs contain bone‐fide LN‐resident innate immune populations, with minimal contamination of blood material. Examination of these populations reveals unique biology not predictable from equivalent blood‐derived populations. LN FNA supernatants represent a specific source of lymph‐ and lymph node‐derived proteins, and can, aided by transcriptomics, identify likely receptor–ligand interactions. This represents the first description of the types and abundance of immune cell populations and cell‐free proteins that can be efficiently studied by LN FNA. These findings are of broad utility for understanding LN physiology in health and disease, including infectious or autoimmune perturbations, and in the case of cervical nodes, neuroscience. [ABSTRACT FROM AUTHOR]

Replication‐incompetent adenovirus (Ad) vector and mRNA‐lipid nanoparticle (LNP) constructs represent two modular vaccine platforms that have attracted substantial interest over the past two decades. Due to the COVID‐19 pandemic and the rapid development of multiple successful vaccines based on these technologies, there is now clear real‐world evidence of the utility and efficacy of these platforms. Considerable optimization and refinement efforts underpin the successful application of these technologies. Despite this, our understanding of the specific pathways and processes engaged by these vaccines to stimulate the immune response remains incomplete. This review will synthesize our current knowledge of the specific mechanisms by which CD8+ T cell and antibody responses are induced by each of these vaccine platforms, and how this can be impacted by specific vaccine construction techniques. Key gaps in our knowledge are also highlighted, which can hopefully focus future studies. [ABSTRACT FROM AUTHOR]

Adenovirus vectors activate V 2+ T cells in a type I interferon-, TNF-, and IL-18-dependent manner V 2 SP + sp T cells are unconventional T cells that can be activated by cytokines without TCR signaling. We examined three species C vectors (Ad5, Ad6, and ChAdN13) and five non-species C vectors (Ad24, Ad35, ChAd63, ChAd68, and ChAdOx1), and found that on average, the non-species C vectors induced significantly more V 2 SP + sp T cell IFN- production (Fig. Adenovirus vaccine vectors activated V 2 SP + sp T cells in an interleukin 18-, TNF-, and type I interferon-dependent manner. [Extracted from the article]

In animal models, brain neurodegeneration biomarkers drain into cervical lymph nodes (CLNs), and this drainage function is reduced with ageing. If this occurred in humans, CLNs may provide a readily accessible measure of this aspect of protein clearance. We tested this hypothesis in people using ultrasound-guided fine needle aspiration. We measured amyloid-beta 40 and 42, phosphorylated tau 181 (pTau181), glial fibrillary acidic protein and neurofilament light using single molecule array in CLN aspirates and plasma from: (i) a discovery cohort of 25 autoimmune patients; and (ii) plasma, CLNs and capillary blood in four healthy volunteers, an optimization cohort. Ultrasound-guided fine needle aspiration was well-tolerated by all participants. In both cohorts, all biomarkers were detected in all plasma and CLN samples, other than neurofilament light (8/17 of discovery cohort). CLN biomarker concentrations were significantly greater than plasma concentrations for all except neurofilament light, most markedly for pTau181 (266-fold; P < 0.02), whose CLN concentrations decreased with age (Spearman r = -0.66, P = 0.001). This study presents the first evidence that neurodegenerative biomarkers are detectable in human CLNs. Raised CLN:plasma biomarker ratios suggest their concentration in CLNs may offer a distinct compartment for minimally-invasive measurement of brain clearance and lymphatic drainage, with potential applicability to study of ageing and future clinical trials., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

CD4 + T cells have been established as central orchestrators of cellular and humoral immune responses to infection or vaccination. However, the need for CD4 + T cell help to generate primary CD8 + T cell responses is variable depending on the infectious agent or vaccine and yet consistently required for the recall of CD8 + T cell memory responses or antibody responses. Given the deployment of new vaccine platforms such as nucleoside-modified mRNA vaccines, we sought to elucidate the requirement for CD4 + T cell help in the induction of cellular and antibody responses to mRNA and adenovirus (Ad)-vectored vaccines against SARS-CoV-2. Using antibody-mediated depletion of CD4 + T cells in a mouse immunization model, we observed that CD4 + T cell help was dispensable for both primary and secondary CD8 + T cell responses to the BNT162b2 and mRNA-1273 mRNA vaccines but required for the AZD1222 Ad-vectored vaccine. Nonetheless, CD4 + T cell help was needed by both mRNA and Ad-vectored vaccine platforms for the generation of antibodies, demonstrating the centrality of CD4 + T cells in vaccine-induced protective immunity against SARS-CoV-2. Ultimately, this highlights the shared and distinct regulation of humoral and cellular responses induced by these vaccine platforms., (© 2024 The Author(s). European Journal of Immunology published by Wiley‐VCH GmbH.)

Vδ2 + γδT cells are unconventional T cells that can be activated by cytokines without TCR signaling. Adenovirus vaccine vectors activated Vδ2 + γδT cells in an interleukin 18-, TNF-, and type I interferon-dependent manner. This stimulatory capacity was associated with adenovirus vectors of non-species C origin, including the ChAdOx1 vaccine platform., (© 2022 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.)