Lymphatic transport shapes the homeostatic immune repertoire of lymph nodes (LNs). LN-resident memory T cells (T) play an important role in site-specific immune memory, yet how LN T form de novo after viral infection remains unclear. Here, we tracked the anatomical distribution of antiviral CD8 T cells as they seeded skin and LN T using a model of vaccinia virus-induced skin infection. LN T localized to the draining LNs (dLNs) of infected skin, and their formation depended on the lymphatic egress of effector CD8 T cells from the skin, already poised for residence. Effector CD8 T cell transit through skin was required to populate LN T in dLNs, a process reinforced by antigen encounter in skin. Furthermore, LN T were protective against viral rechallenge in the absence of circulating memory T cells. These data suggest that a subset of tissue-infiltrating CD8 T cells egress from tissues during viral clearance and establish a layer of regional protection in the dLN basin.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1126/sciimmunol.adk8141 | DOI Listing |
"Active" reservoir cells transcribing HIV can perpetuate chronic inflammation in virally suppressed people with HIV (PWH) and likely contribute to viral rebound after antiretroviral therapy (ART) interruption, so they represent an important target for new therapies. These cells, however, are difficult to study using single-cell RNA-seq (scRNA-seq) due to their low frequency and low levels of HIV transcripts, which are usually not polyadenylated. Here, we developed "HIV-seq" to enable more efficient capture of HIV transcripts - including non-polyadenylated ones - for scRNA-seq analysis of cells from PWH.
View Article and Find Full Text PDFUnlabelled: The persistence of HIV-1 reservoirs during combination anti-retroviral therapy (cART) leads to chronic immune activation and systemic inflammation in people with HIV (PWH), associating with a suboptimal immune reconstitution as well as an increased risk of non-AIDS events. This highlights the needs to develop novel therapy for HIV-1 related diseases in PWH. In this study, we assessed the therapeutic effect of CD24-Fc, a fusion protein with anti-inflammatory properties that interacts with danger-associated molecular patterns (DAMPs) and siglec-10, in chronic HIV-1 infection model using humanized mice undergoing suppressive cART.
View Article and Find Full Text PDFTranscription repressor BACH2 redirects short-lived terminally differentiated effector into long-lived memory cells. We postulate that BACH2-mediated long-lived memory programs promote HIV-1 persistence in gut CD4+ T cells. We coupled single-cell DOGMA-seq and TREK-seq to capture chromatin accessibility, transcriptome, surface proteins, T cell receptor, HIV-1 DNA and HIV-1 RNA in 100,744 gut T cells from ten aviremic HIV-1+ individuals and five HIV-1- donors.
View Article and Find Full Text PDFUnlabelled: Despite recent advances, the regulation of anticancer and antimicrobial bioactive compound (AABC) production by leukocytes remains poorly understood. Here, we demonstrate that inactivation of the DNA- and RNA-based Teazeled receptors of the Universal Receptive System in human leukocytes generated so called "Leukocyte-Tells," which showed enhanced AABC production. Comprehensive analysis of the AABCs produced by Leukocyte-Tells based on LC/MS identified 707 unique or differentially produced peptide or non-peptide metabolites.
View Article and Find Full Text PDFBackground: Bispecific T cell-engagers (BTEs) are engineered antibodies that redirect T cells to target antigen-expressing tumors. BTEs targeting various tumor-specific antigens, like interleukin 13 receptor alpha 2 (IL13RA2) and EGFRvIII, have been developed for glioblastoma (GBM). However, limited knowledge of BTE actions derived from studies conducted in immunocompromised animal models impedes progress in the field.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!