17 research outputs found

    Memory CD8(+) T cell heterogeneity is primarily driven by pathogen-specific cues and additionally shaped by the tissue environment

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    Factors that govern the complex formation of memory T cells are not completely understood. A better understanding of the development of memory T cell heterogeneity is however required to enhance vaccination and immunotherapy approaches. Here we examined the impact of pathogen- and tissue-specific cues on memory CD8(+) T cell heterogeneity using high-dimensional single-cell mass cytometry and a tailored bioinformatics pipeline. We identified distinct populations of pathogen-specific CD8(+) T cells that uniquely connected to a specific pathogen or associated tomultiple types of acute and persistent infections. In addition, the tissue environment shaped the memory CD8(+) T cell heterogeneity, albeit to a lesser extent than infection. The programming of memory CD8(+) T cell differentiation during acute infection is eventually superseded by persistent infection. Thus, the plethora of distinct memory CD8(+) T cell subsets that arise upon infection is dominantly sculpted by the pathogen-specific cues and further shaped by the tissue environment.Radiolog

    Chemically engineered glycan-modified cancer vaccines to mobilize skin dendritic cells

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    Dendritic cell (DC)ā€“targeting vaccines show great promise in increasing antitumor immunity. Glycan-engineered vaccines facilitate both DC targeting and increased uptake by DCs for processing and presentation to CD4+ and CD8+ T cells to induce tumor-specific T-cell responses. However, the complexity of various DC subsets in skin tissues, expressing different glycan-binding receptors that can mediate vaccine uptake or drainage of vaccines via lymphatics directly to the lymph nodeā€“resident DCs, complicates the success of vaccines. Moreover, the influx of inflammatory immune cells to the site of vaccination, such as monocytes that differentiate to DCs and coexpress glycan-binding receptors, may contribute to the strength of DC-targeting glycovaccines for future clinical use

    Memory CD8<sup>+</sup> T cell heterogeneity is primarily driven by pathogen-specific cues and additionally shaped by the tissue environment

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    SummaryFactors that govern the complex formation of memory T cells are not completelyunderstood. A better understanding of thedevelopment of memory Tcell hetero-geneity is however required to enhance vaccination and immunotherapy ap-proaches. Here we examined the impact of pathogen- and tissue-specific cueson memory CD8+T cell heterogeneity using high-dimensional single-cell mass cy-tometry and a tailored bioinformatics pipeline. We identified distinct populationsof pathogen-specific CD8+T cells that uniquely connected to a specific pathogenor associated to multiple types of acute and persistent infections. In addition, thetissue environment shaped the memory CD8+T cell heterogeneity, albeit to alesser extent than infection. The programming of memory CD8+T cell differenti-ation during acute infection is eventually superseded by persistent infection.Thus, the plethora of distinct memory CD8+T cell subsets that arise upon infec-tion is dominantly sculpted by the pathogen-specific cues and further shaped by the tissue environment.Pattern Recognition and Bioinformatic
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