Article
Immunology
Sabrina Pollastro, Marie de Bourayne, Giulia Balzaretti, Aldo Jongejan, Barbera D. C. van Schaik, Ilse T. G. Niewold, Antoine H. C. van Kampen, Bernard Maillere, Niek de Vries
Summary: The study demonstrated a new method to identify and characterize antigen-responsive T cell clones using high-throughput T-cell receptor repertoire sequencing. By combining datasets and a novel analysis protocol, the researchers successfully explored the dynamics of T cell clonal expansion and antigen response characteristics.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Annekathrin Silvia Nedwed, Sara Salome Helbich, Kathrin Luise Braband, Michael Volkmar, Michael Delacher, Federico Marini
Summary: This article introduces the methods for single-cell gene expression analysis, T-cell receptor clonality, and cell surface protein expression using sequencing. It also describes the isolation of scRNA/TCR-seq-compatible CD4(+) T cells from murine tissues and provides a step-by-step bioinformatic analysis pipeline for sequencing data. The article demonstrates the quantification of gene expression, extraction of T-cell receptor sequences, quality control, and visualization of results.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biology
Gerdien Mijnheer, Nila Hendrika Servaas, Jing Yao Leong, Arjan Boltjes, Eric Spierings, Phyllis Chen, Liyun Lai, Alessandra Petrelli, Sebastiaan Vastert, Rob J. de Boer, Salvatore Albani, Aridaman Pandit, Femke van Wijk, Di Chen
Summary: Autoimmune inflammation is characterized by tissue infiltration and expansion of antigen-specific T cells. In this study, the authors used CyTOF analysis and TCR sequencing to investigate the immune cell composition and expansion of specific T cell clones in juvenile idiopathic arthritis (JIA). They found that the infiltrates in different affected joints of the same patient were similar, and dominant T cell clones, including Tregs, persisted over time. These findings suggest the presence of autoantigen-driven expansion of T cell clones in localized autoimmune disease.
Article
Immunology
Elena I. Kovalenko, Ivan V. Zvyagin, Maria A. Streltsova, Artem I. Mikelov, Sofya A. Erokhina, William G. Telford, Alexander M. Sapozhnikov, Yury B. Lebedev
Summary: The study found that T cells expressing NKG2C in CD56(+) subset are highly differentiated and produce almost no IFN-gamma in response to HCMV stimulation, with their frequency positively correlated with NKG2C(+) NK cell frequency.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Toxicology
Sean Hammond, Xiaoli Meng, Merrie Mosedale, Dean J. Naisbitt
Summary: Tolvaptan is effective for treating polycystic kidney disease, but its use carries a risk of T-cell-mediated liver injury. After contraindication, the tolerance of similar drugs with similar pharmacological actions and structures is a clinical challenge. In this study, tolvaptan-responsive T-cell clones were exposed to similar pharmaceutical agents, and it was found that mozavaptan induced a comparable immune response as tolvaptan, suggesting potential immunological intolerance.
TOXICOLOGY LETTERS
(2023)
Article
Immunology
Constantin Aschauer, Kira Jelencsics, Karin Hu, Andreas Heinzel, Mariella Gloria Gregorich, Julia Vetter, Susanne Schaller, Stephan M. Winkler, Johannes Weinberger, Lisabeth Pimenov, Guido A. Gualdoni, Michael Eder, Alexander Kainz, Anna Regina Troescher, Heinz Regele, Roman Reindl-Schwaighofer, Thomas Wekerle, Johannes Bernhard Huppa, Megan Sykes, Rainer Oberbauer
Summary: Sequencing of T-cell receptor repertoires in kidney transplant recipients revealed an enrichment of donor-reactive T-cells in the allograft during TCMR episodes, with dominant tissue clones also found in the blood. This study suggests an unchoreographed process of diverse T-cell clones directed against numerous non-self antigens in the transplanted organ.
FRONTIERS IN IMMUNOLOGY
(2021)
Editorial Material
Immunology
Klaas P. J. M. van Gisbergen, Carmen Gerlach
Summary: The expansion capacity of naive T cells is believed to be the main factor determining the magnitude of CD8 T-cell responses against intracellular pathogens. However, a study challenges this notion and reveals that the recruitment of naive T-cell clones into primary responses can be incomplete, especially when there are low-affinity interactions between the T-cell receptor and the pathogen's antigen. This research shows that the regulation of CD8 T-cell response size involves control at the level of recruitment and expansion of naive CD8 T cells.
EUROPEAN JOURNAL OF IMMUNOLOGY
(2023)
Article
Immunology
Giovanna Linguiti, Vincenzo Tragni, Ciro Leonardo Pierri, Serafina Massari, Marie-Paule Lefranc, Rachele Antonacci, Salvatrice Ciccarese
Summary: This study investigates the 3D structure of human and dromedary γδ T cell receptors to understand how they recognize antigen in an antibody-like fashion. The results show that the interactions between the V domains of TRG and TRD, as well as between the V domains and CD1D G domains, are stable.
FRONTIERS IN IMMUNOLOGY
(2022)
Editorial Material
Hematology
Andreas Greinacher, Falk Nimmerjahn
Summary: In this article published in Blood, Wang et al. demonstrate that the severe adverse effect of vaccine-induced immune thrombotic thrombocytopenia (VITT) is caused by structurally similar antibodies. Their findings suggest that VITT is the result of rapid clonal expansion of a few B-cell clones, leading to the production of a few closely related antibodies. Furthermore, the gene encoding the variable region of the immunoglobulin G (IgG) light chain appears to have the same polymorphism (IGLV3-21*02) in all patients investigated.
Article
Immunology
Ulrike Gerdemann, Ryan A. Fleming, James Kaminski, Connor McGuckin, Xianliang Rui, Jennifer F. Lane, Paula Keskula, Lorenzo Cagnin, Alex K. Shalek, Victor Tkachev, Leslie S. Kean
Summary: The new RM-scTCR-Seq pipeline enables the amplification, reconstruction, and pairing of RM-specific single-cell TCRs with their transcriptional profiles for the first time. This method allows for the identification and tracking of alloreactive clonotypes detected in RM, as well as exploration of their GVHD-driven cytotoxic T cell characteristics in target organs. This novel platform fundamentally advances the utility of RM in studying protective and pathogenic T cell responses.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Rheumatology
Celine Lamacchia, Zuleika Calderin Sollet, Delphine Courvoisier, Denis Mongin, Gaby Palmer, Oliva Studer, Cem Gabay, Jean Villard, Stephane Buhler, Axel Finckh
Summary: In this study, it was found that highly expanded clones (HEC) were detected in the peripheral blood before the clinical onset of rheumatoid arthritis (RA), particularly in the later pre-clinical phase of RA development, and their presence increased over time.
Article
Immunology
Katharina Deschler, Judith Rademacher, Sonja M. Lacher, Alina Huth, Markus Utzt, Stefan Krebs, Helmut Blum, Hildrun Haibel, Fabian Proft, Mikhail Protopopov, Valeria Rios Rodriguez, Eduardo Beltran, Denis Poddubnyy, Klaus Dornmair
Summary: This study investigated the T cell receptor (TCR) usage and whole transcriptomes of CD8+ single cells to analyze the pathogenesis of Spondyloarthritis (SpA). The findings suggest that (auto)antigenic peptides may play a role in the development of SpA.
JOURNAL OF AUTOIMMUNITY
(2022)
Article
Immunology
Darina Paprckova, Veronika Niederlova, Alena Moudra, Ales Drobek, Michaela Pribikova, Sarka Janusova, Kilian Schober, Ales Neuwirth, Juraj Michalik, Martina Huranova, Veronika Horkova, Michaela Cesnekova, Michaela Simova, Jan Prochazka, Jana Balounova, Dirk H. Busch, Radislav Sedlacek, Martin Schwarzer, Ondrej Stepanek
Summary: Mature T cells are selected in the thymus for their ability to recognize self-antigens, but the role of self-reactivity in T-cell biology is still not fully understood. By examining mouse peripheral CD8(+) T cells, two unconventional populations of antigen-inexperienced T cells were discovered. Highly self-reactive T cells preferentially differentiate into antigen-inexperienced memory-like cells, but do not form a population expressing specific genes.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Natalia Fernandez, Peter Hayes, Julia Makinde, Jonathan Hare, Deborah King, Rui Xu, Ola Rehawi, Allison T. Mezzell, Laban Kato, Susan Mugaba, Jennifer Serwanga, James Chemweno, Eunice Nduati, Matt A. Price, Faith Osier, Christina Ochsenbauer, Ling Yue, Eric Hunter, Jill Gilmour
Summary: This study describes a functional viral inhibition assay to evaluate the CD8 T-cell-mediated inhibition of HIV-1 replication. The assay was successfully established across multiple clinical research centers and showed reproducibility. This method provides a tool for designing HIV-1 vaccine candidates and evaluating vaccine-induced T-cell immune responses in clinical trials.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Hematology
Amna Malik, Anwar A. Sayed, Panpan Han, Michelle M. H. Tan, Eleanor Watt, Adela Constantinescu-Bercu, Alexander T. H. Cocker, Ahmad Khoder, Rocel C. Saputil, Emma Thorley, Ariam Teklemichael, Yunchuan Ding, Alice C. J. Hart, Haiyu Zhang, Wayne A. Mitchell, Nesrina Imami, James T. B. Crawley, Isabelle I. Salles-Crawely, James B. Bussel, James L. Zehnder, Stuart Adams, Bing M. Zhang, Nichola Cooper
Summary: This study investigates the role of cytotoxic CD8(+) T cells in ITP and finds that adults with chronic ITP have increased polyfunctional TEMRA cells expressing interferon gamma, tumor necrosis factor a, and granzyme B. TCR sequencing shows expanded T-cell clones in patients with ITP, which persist over many years and are more prominent in refractory cases. In vitro experiments demonstrate that CD8(+) T cells from patients with ITP form aggregates with autologous platelets, release interferon gamma, and trigger platelet activation and apoptosis via TCR-mediated release of cytotoxic granules.