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Sharpe and colleagues devise a conditional gene deletion model in mice for rapid sequential, combinatorial and lineage-specific interrogation of gene function in hematopoietic cells.
Coukos, Corria-Osorio and colleagues use an orthogonal genetic approach to engineer CD8+ T cells into better effector synthetic cells for antitumor adoptive cell therapy. This approach generates engineered effector T cells that express an IL-2 variant, IL-33 and a programmed cell death protein 1 decoy.
Dalod and colleagues utilize a combinatorial genetic reporter strategy to uniquely mark plasmacytoid dendritic cells (pDCs) in mice. They utilize these mice to identify bona fide pDCs and functionally characterize before and during viral infection, in comparison to several other DC types.
Sieweke and colleagues show that alveolar macrophages maintain a core gene expression program even after several months in culture and reacquire full transcriptional and epigenetic identity after transplantation into the lung.
Choe and colleagues show that intravital three-photon microscopy can be used to visualize the popliteal LN in mice and measure CD8+ T cells and CD4+ T cell motility through this paper shows T cell motility in the entire depthof T cell zone by ~635 um.
Jiang and colleagues describe a high-dimensional, high-throughput tetramer-associated TCR sequencing (TetTCR-SeqHD) method to simultaneously profile TCR sequences, cognate antigen specificities, targeted gene expression and surface-protein expression from tens of thousands of single cells.
Accurate serology testing is urgently needed to help diagnose SARS-CoV-2 infection. Here Valkenburg and colleagues use a luciferase immunoprecipitation system to assess the antibody responses to 15 different SARS-CoV-2 antigens in patients with COVID-19 and find ORF8 and ORF3b antibodies, taken together as a cluster of points, identified 96.5% of COVID-19 samples at early and late time points of disease with 99.5% specificity
Current high-throughput 3′ single-cell RNA-sequencing (scRNA-seq) techniques are limited in their ability to elucidate the variable sequences of antigen receptors. Love and colleagues describe a strategy that enables simultaneous analysis of TCR sequences and the corresponding full transcriptomes from 3′-barcoded scRNA-seq samples.
Tissue-resident memory T (TRM) cells have been studied mainly in mouse models. Schumacher and colleagues have developed an imaging technology to track in real time skin-resident human CD8+ TRM cells in situ.
Determining TCR specificity represents a formidable technical barrier to the harnessing of T cell function. Kisielow and colleagues describe a novel platform for efficient determination of TCR specificities in a variety of infectious and cancer settings and in both human systems and mouse systems.
It remains difficult to distinguish cognate APC–T cell interactions in human tissue sections. Clark and colleagues have developed an imaging–machine-learning pipeline that uses deep convolutional and tuned neural networks to identify the combination of distance and cell-shape features that can discriminate between bystander human APC–T cell interactions and cognate interactions in situ.
Isolating tissue-resident cells runs the risk of altering their expression profile. Jung and colleagues use a RiboTagging approach to describe the microglial translatome and demonstrate that macrophage extraction from their tissue environment results in significant transcriptional alterations.