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Cheru N, Hafler DA, Sumida TS
Frontiers in immunology. May 18, 2023
PMID: 37197653
Autoimmune Diseases
HIPC 3 (2022)
immune interaction
Immune Tolerance
Regulatory T cells (Tregs)
tissue resident
Yale University
Abstract:
Maintenance of peripheral tolerance by CD4
Solomon BD, Zheng H, Dillon LW, Goldman JD, Hourigan CS, Heath JR, Khatri P
Frontiers in immunology. May 14, 2023
PMID: 37180102
allele specific expression
HIPC 3 (2022)
HLA genotype
HLA typing algorithm
human leukocyte antigen (HLA)
major histocompatibility (MHC)
next-generation sequencing data (NGS)
single-cell sequencing (scRNA-seq)
Stanford
Abstract:
The human leukocyte antigen (HLA) locus plays a central role in adaptive immune function and has significant clinical implications for tissue transplant compatibility and allelic disease associations. Studies using bulk-cell RNA sequencing have demonstrated that HLA transcription may be regulated in an allele-specific manner and single-cell RNA sequencing (scRNA-seq) has the potential to better characterize these expression patterns. However, quantification of allele-specific expression (ASE) for HLA loci requires sample-specific reference genotyping due to extensive polymorphism. While genotype prediction from bulk RNA sequencing is well described, the feasibility of predicting HLA genotypes directly from single-cell data is unknown. Here we evaluate and expand upon several computational HLA genotyping tools by comparing predictions from human single-cell data to gold-standard, molecular genotyping. The highest 2-field accuracy averaged across all loci was 76% by arcasHLA and increased to 86% using a composite model of multiple genotyping tools. We also developed a highly accurate model (AUC 0.93) for predicting
Tippalagama R, Chihab LY, Kearns K, Lewis S, Panda S, Willemsen L, Burel JG, Lindestam Arlehamn CS
Frontiers in immunology. May 1, 2023
PMID: 37122719
Adaptive Immunity
antigen specificity
HIPC 3 (2022)
La Jolla Institute for Immunology
sequencing
T cells
TCR
Abstract:
Antigen-specific T cells play a central role in the adaptive immune response and come in a wide range of phenotypes. T cell receptors (TCRs) mediate the antigen-specificities found in T cells. Importantly, high-throughput TCR sequencing provides a fingerprint which allows tracking of specific T cells and their clonal expansion in response to particular antigens. As a result, many studies have leveraged TCR sequencing in an attempt to elucidate the role of antigen-specific T cells in various contexts. Here, we discuss the published approaches to studying antigen-specific T cells and their specific TCR repertoire. Further, we discuss how these methods have been applied to study the TCR repertoire in various diseases in order to characterize the antigen-specific T cells involved in the immune control of disease.
Arunachalam PS, Lai L, Samaha H, Feng Y, Hu M, Hui HS, Wali B, Ellis M, Davis-Gardner ME, Huerta C, Bechnak K, Bechnak S, Lee M, Litvack MB, Losada C, Grifoni A, Sette A, Zarnitsyna VI, Rouphael N, Suthar MS, Pulendran B
The Journal of clinical investigation. March 24, 2023
PMID: 36951954
Adaptive Immunity
HIPC 3 (2022)
Stanford
Vaccines
Abstract:
BackgroundMaintaining durable immunity following vaccination represents a major challenge, but whether mRNA booster vaccination improves durability is unknown.MethodsWe measured antibody responses in 55 healthy adults, who received a booster dose of the Pfizer-BioNTech or Moderna vaccine against SARS-CoV-2 and calculated the half-life of the antibody titers. We also measured memory B and T cell responses in a subset of 28 participants. In 13 volunteers who received a second booster vaccine, we measured serum antibody titers and memory B and T cell responses.ResultsThe booster (third immunization) dose at 6 to 10 months increased the half-life of the serum-neutralizing antibody (nAb) titers to 76 days from 56 to 66 days after the primary 2-dose vaccination. A second booster dose (fourth immunization) a year after the primary vaccination further increased the half-life to 88 days. However, despite this modestly improved durability in nAb responses against the ancestral (WA.1) strain, there was a loss of neutralization capacity against the Omicron subvariants BA.2.75.2, BQ.1.1, and XBB.1.5 (48-, 71-, and 66-fold drop in titers, respectively, relative to the WA.1 strain). Although only 45% to 65% of participants demonstrated a detectable nAb titer against the newer variants after the booster (third dose), the response declined to below the detection limit in almost all individuals by 6 months. In contrast, booster vaccination induced antigen-specific memory B and T cells that persisted for at least 6 months.ConclusionThe durability of serum antibody responses improves only marginally following booster immunizations with the Pfizer-BioNTech or Moderna mRNA vaccines.
Krammer F, Schultz-Cherry S
Nature reviews. Immunology. March 23, 2023
PMID: 36944755
HIPC 3 (2022)
Icahn School of Medicine at Mount Sinai
Abstract:
H5N1 avian influenza viruses of the A/goose/Guangdong/1/96 lineage have been circulating in wild birds for many years, have inflicted significant economic losses on the poultry industry and have caused zoonotic infections since 1997. However, the recent spread of avian H5N1 virus to the Americas and its detection in mammals have raised concerns about its pandemic potential.
Recent evidence of transmission of avian H5N1 viruses among mammals raises concerns about their pandemic potential. We need to increase our awareness and preparedness, and should also be thinking about safe farming practices to prevent the emergence of concerning pathogens in the future.
Rancan C, Arias-Badia M, Dogra P, Chen B, Aran D, Yang H, Luong D, Ilano A, Li J, Chang H, Kwek SS, Zhang L, Lanier LL, Meng MV, Farber DL, Fong L
Nature immunology. March 18, 2023
PMID: 36928415
Columbia University
HIPC 3 (2022)
Abstract:
Gamma delta (γδ) T cells reside within human tissues including tumors, but their function in mediating antitumor responses to immune checkpoint inhibition is unknown. Here we show that kidney cancers are infiltrated by Vδ2
Wanjalla CN, Gabriel CL, Fuseini H, Bailin SS, Mashayekhi M, Simmons J, Warren CM, Glass DR, Oakes J, Gangula R, Wilfong E, Priest S, Temu T, Newell EW, Pakala S, Kalams SA, Gianella S, Smith D, Harrison DG, Mallal SA, Koethe JR
Frontiers in immunology. March 4, 2023
PMID: 36865544
cardiometabolic disease
CD4 T cells
CGC
Cytomegalovirus
HIPC 3 (2022)
HIV
Seattle Children's Research Institute
Abstract:
Persons with HIV (PWH) on long-term antiretroviral therapy (ART) have a higher incidence and prevalence of cardiometabolic diseases attributed, in part, to persistent inflammation despite viral suppression. In addition to traditional risk factors, immune responses to co-infections such as cytomegalovirus (CMV) may play an unappreciated role in cardiometabolic comorbidities and offer new potential therapeutic targets in a subgroup of individuals. We assessed the relationship of CX3CR1
Côrte-Real BF, Hamad I, Arroyo Hornero R, Geisberger S, Roels J, Van Zeebroeck L, Dyczko A, van Gisbergen MW, Kurniawan H, Wagner A, Yosef N, Weiss SNY, Schmetterer KG, Schröder A, Krampert L, Haase S, Bartolomaeus H, Hellings N, Saeys Y, Dubois LJ, Brenner D, Kempa S, Hafler DA, Stegbauer J, Linker RA, ...
Cell metabolism. Feb. 9, 2023
PMID: 36754020
Autoimmunity
FOXP3
high salt
HIPC 3 (2022)
mitochondrial respiration
regulatory T cells
Yale University
Abstract:
FOXP3
Hillman H, Khan N, Singhania A, Dubelko P, Soldevila F, Tippalagama R, DeSilva AD, Gunasena B, Perera J, Scriba TJ, Ontong C, Fisher M, Luabeya A, Taplitz R, Seumois G, Vijayanand P, Hedrick CC, Peters B, Burel JG
Frontiers in immunology. Jan. 31, 2023
PMID: 36713384
Flow Cytometry
HIPC 3 (2022)
immune signatures
La Jolla Institute for Immunology
Monocytes
transcriptomics (RNA-Seq)
Tuberculosis
Abstract:
Previous studies suggest that monocytes are an important contributor to tuberculosis (TB)-specific immune signatures in blood.
Here, we carried out comprehensive single-cell profiling of monocytes in paired blood samples of active TB (ATB) patients at diagnosis and mid-treatment, and healthy controls.
At diagnosis, ATB patients displayed increased monocyte-to-lymphocyte ratio, increased frequency of CD14+CD16- and intermediate CD14+CD16+ monocytes, and upregulation of interferon signaling genes that significantly overlapped with previously reported blood TB signatures in both CD14+ subsets. In this cohort, we identified additional transcriptomic and functional changes in intermediate CD14+CD16+ monocytes, such as the upregulation of inflammatory and MHC-II genes, and increased capacity to activate T cells, reflecting overall increased activation in this population. Single-cell transcriptomics revealed that distinct subsets of intermediate CD14+CD16+ monocytes were responsible for each gene signature, indicating significant functional heterogeneity within this population. Finally, we observed that changes in CD14+ monocytes were transient, as they were no longer observed in the same ATB patients mid-treatment, suggesting they are associated with disease resolution.
Together, our study demonstrates for the first time that both intermediate and classical monocytes individually contribute to blood immune signatures of ATB and identifies novel subsets and associated gene signatures that may hold disease relevance.
Poon MML, Caron DP, Wang Z, Wells SB, Chen D, Meng W, Szabo PA, Lam N, Kubota M, Matsumoto R, Rahman A, Luning Prak ET, Shen Y, Sims PA, Farber DL
Nature immunology. Jan. 20, 2023
PMID: 36658238
Columbia University
HIPC 3 (2022)
Abstract:
T lymphocytes migrate to barrier sites after exposure to pathogens, providing localized immunity and long-term protection. Here, we obtained blood and tissues from human organ donors to examine T cells across major barrier sites (skin, lung, jejunum), associated lymph nodes, lymphoid organs (spleen, bone marrow), and in circulation. By integrating single-cell protein and transcriptome profiling, we demonstrate that human barrier sites contain tissue-resident memory T (T
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Last updated: 2023-05-30 18:30