Article
Immunology
Ambra Natalini, Sonia Simonetti, Gabriele Favaretto, Lorenzo Lucantonio, Giovanna Peruzzi, Miguel Munoz-Ruiz, Gavin Kelly, Alessandra M. Contino, Roberta Sbrocchi, Simone Battella, Stefania Capone, Antonella Folgori, Alfredo Nicosia, Angela Santoni, Adrian C. Hayday, Francesca Di Rosa
Summary: The responsiveness of memory CD8 T cells to secondary antigenic challenge varies at different times after a primary response. Understanding the molecular mechanisms underlying this changing responsiveness can improve the secondary response of memory CD8 T cells.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Zihang Chen, Qiqi Zhu, Xueqin Deng, Wenqing Yao, Wenyan Zhang, Weiping Liu, Yuan Tang, Sha Zhao
Summary: CD8-predominant AITL is a distinct immune pattern of AITL characterized by anti-tumor immunity impairment and an immunosuppressive microenvironment. CD8-predominant AITL shows significant differences compared to common AITL in terms of clinical and pathological features, TIL subsets, immunoglobulin heavy chain (IGH) repertoires, and gene expression profiles. These characteristics may explain its severe clinical manifestations and poor prognosis.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Jonathan B. Johnnidis, Yuki Muroyama, Shin Foong Ngiow, Zeyu Chen, Sasikanth Manne, Zhangying Cai, Shufei Song, Jesse M. Platt, Jason M. Schenkel, Mohamed Abdel-Hakeem, Jean-Christophe Beltra, Allison R. Greenplate, Mohammed-Alkhatim A. Ali, Kito Nzingha, Josephine R. Giles, Christelle Harly, John Attanasio, Kristen E. Pauken, Bertram Bengsch, Michael A. Paley, Vesselin T. Tomov, Makoto Kurachi, Dario A. A. Vignali, Arlene H. Sharpe, Steven L. Reiner, Avinash Bhandoola, F. Bradley Johnson, E. John Wherry
Summary: The study identifies a distinct subset of memory T cells during the expansion phase of acute viral infection, which possess unique characteristics and play an important role in CD8(+) T cell memory. This subset, although quantitatively minor in the TCF-1(+) pool, exhibits self-renewal and long-term recall capacity.
SCIENCE IMMUNOLOGY
(2021)
Article
Immunology
Jiri Koutnik, Michael Leitges, Kerstin Siegmund
Summary: This study investigated the role of PKD3 in T cell activation and found that it is dispensable for T cell activation. The skewing in the T cell compartment observed in conventional PKD3-deficient mice seems to be mediated by T cell-extrinsic mechanisms.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Lauren Daniel, Marion Tassery, Clara Lateur, Antoine Thierry, Andre Herbelin, Jean-Marc Gombert, Alice Barbarin
Summary: Immunosenescence is a physiological process associated with changes in the immune system, particularly involving CD8 T cells. The newly described innate E(+) CD8 T cells may exhibit an exacerbated senescent phenotype in a chronic inflammatory environment, especially in kidney transplant and cytomegalovirus-infected patients.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Joseph S. Dolina, Joey Lee, Eugene L. Moore, Jennifer L. Hope, Donald T. Gracias, Takaji Matsutani, Ashu Chawla, Jason A. Greenbaum, Joel Linden, Stephen P. Schoenberger
Summary: During acute infection, CD4(+) regulatory T cells play a crucial role in regulating the immune response by suppressing cytotoxic CD8(+) T lymphocytes through different mechanisms. Early T cells inhibit primary CTL expansion through adenosine production, while late-phase T-regs suppress T cell proliferation through the transfer of cAMP. This study reveals the distinct roles of different T-reg lineages in fine-tuning CTL priming and contraction phases during acute infection.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Seong Jin Choi, June-Young Koh, Min-Seok Rha, In-Ho Seo, Hoyoung Lee, Seongju Jeong, Su-Hyung Park, Eui-Cheol Shin
Summary: Subsets of human CD8+ T cells express inhibitory NK cell receptors, KIRs and NKG2A. These receptors are mutually exclusive in their expression and have distinct phenotypic and functional characteristics. KIR+CD8+ T cells are more differentiated, senescent, and responsive to IL2R8, while NKG2A+CD8+ T cells are more responsive to IL12R81, IL12R82, and IL18R8, and exhibit strong IFN-g production and NK-like cytotoxicity in response to IL-15.
Article
Virology
Julia M. DeRogatis, Emily N. Neubert, Karla M. Viramontes, Monique L. Henriquez, Dequina A. Nicholas, Roberto Tinoco
Summary: CD38 expression regulates the survival and metabolism of CD8(+) T cells during acute and chronic viral infections. Higher CD38 levels are observed during chronic infection, leading to T cell exhaustion. CD38 has a dual cell-intrinsic function in limiting proliferation and function while promoting the survival of CD8(+) T cells.
JOURNAL OF VIROLOGY
(2023)
Article
Gastroenterology & Hepatology
Kathrin Heim, Benedikt Binder, Sagar, Dominik Wieland, Nina Hensel, Sian Llewellyn-Lacey, Emma Gostick, David A. Price, Florian Emmerich, Hildegard Vingerhoet, Anke R. M. Kraft, Markus Cornberg, Tobias Boettler, Christoph Neumann-Haefelin, Dietmar Zehn, Bertram Bengsch, Maike Hofmann, Robert Thimme
Summary: TOX expression in HBV-specific CD8+ T cells is associated with chronic antigen stimulation, correlated with viral load, and related to phenotypic and functional characteristics of T-cell exhaustion. The expression of TOX in HBV-specific CD8+ T cells is maintained and indicates a permanent molecular imprint after chronic but not temporary stimulation.
Review
Immunology
Joseph S. Dolina, Natalija Van Braeckel-Budimir, Graham D. Thomas, Shahram Salek-Ardakani
Summary: Recent research has revealed the heterogeneity within the exhausted CD8(+) T cell lineage, which consists of multiple interconnected subpopulations with distinct characteristics and locations. This understanding calls for a re-focusing of cancer immunotherapies on targeting the driver mechanisms underlying CD8(+) T(ex) development to stabilize functional subsets.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Mahrukh A. Huseni, Lifen Wang, Joanna E. Klementowicz, Kobe Yuen, Beatrice Breart, Christine Orr, Li-fen Liu, Yijin Li, Vinita Gupta, Congfen Li, Deepali Rishipathak, Jing Peng, Yasin Senbabaoglu, Zora Modrusan, Shilpa Keerthivasan, Shravan Madireddi, Ying-Jiun Chen, Eleanor J. Fraser, Ning Leng, Habib Hamidi, Hartmut Koeppen, James Ziai, Kenji Hashimoto, Marcella Fasso, Patrick Williams, David F. McDermott, Jonathan E. Rosenberg, Thomas Powles, Leisha A. Emens, Priti S. Hegde, Ira Mellman, Shannon J. Turley, Mark S. Wilson, Sanjeev Mariathasan, Luciana Molinero, Mark Merchant, Nathaniel R. West
Summary: IL-6 is identified as a correlate of poor response to atezolizumab in clinical trials of advanced kidney, breast, and bladder cancers. In pre-clinical models, combined blockade of PD-L1 and IL-6 receptor (IL6R) has synergistic regression effects on tumors and improves anti-tumor CD8+ cytotoxic T lymphocyte (CTL) responses. Agents targeting IL-6 signaling could be potential partners for combination with immune checkpoint inhibitors (ICIs) in cancer patients.
CELL REPORTS MEDICINE
(2023)
Article
Oncology
Philippa Meiser, Moritz A. Knolle, Anna Hirschberger, Gustavo P. de Almeida, Felix Bayerl, Sebastian Lacher, Anna-Marie Pedde, Sophie Flommersfeld, Julian Hoenninger, Leonhard Stark, Fabian Stoegbauer, Martina Anton, Markus Wirth, Dirk Wohlleber, Katja Steiger, Veit R. Buchholz, Barbara Wollenberg, Christina E. Zielinski, Rickmer Braren, Daniel Rueckert, Percy A. Knolle, Georgios Kaissis, Jan P. Boettcher
Summary: A study found that the clustering of immune cells within tumors, orchestrated by a specific type of immune cell called cDC1, is a unique feature associated with effective anti-cancer immunity. These clusters promote the activation and expansion of stem-like CD8+ T cells, which play a crucial role in cancer immune control. This finding has important implications for cancer therapy.
Article
Cell Biology
Qianqian Duan, Jiying Ding, Fangfang Li, Xiaowei Liu, Yunan Zhao, Hongxiu Yu, Yong Liu, Lianjun Zhang
Summary: This study demonstrates that SIRT5 is dispensable for the effector function and memory differentiation of CD8(+) T cells.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Immunology
Maria Elena Maccari, Sebastian Fuchs, Patrick Kury, Geoffroy Andrieux, Simon Volkl, Bertram Bengsch, Myriam Ricarda Lorenz, Maximilian Heeg, Jan Rohr, Sabine Jagle, Carla N. Castro, Miriam Gross, Ursula Warthorst, Christoph Koenig, Ilka Fuchs, Carsten Speckmann, Julian Thalhammer, Friedrich G. Kapp, Markus G. Seidel, Gregor Duckers, Stefan Schoenberger, Catharina Schuetz, Marita Fuhrer, Robin Kobbe, Dirk Holzinger, Christian Klemann, Petr Smisek, Stephen Owens, Gerd Horneff, Reinhard Kolb, Nora Naumann-Bartsch, Maurizio Miano, Julian Staniek, Marta Rizzi, Tomas Kalina, Pascal Schneider, Anika Erxleben, Rolf Backofen, Arif Ekici, Charlotte M. Niemeyer, Klaus Warnatz, Bodo Grimbacher, Hermann Eibel, Andreas Mackensen, Andreas Philipp Frei, Klaus Schwarz, Melanie Boerries, Stephan Ehl, Anne Rensing-Ehl
Summary: The identification and characterization of a population of FAS-controlled TCR alpha beta(+) T cells in autoimmune lymphoproliferative syndrome show numerous unique features, including a distinct molecular signature, high proliferation rates, noncytotoxicity, and IL-10 cytokine bias. Mechanistically, the regulation of this population involves FAS and CTLA4 signaling, as well as mTOR and STAT3 signals, and genetic alterations in these pathways can lead to significant lymphoproliferative disease.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Multidisciplinary Sciences
Sana Hibino, Shotaro Eto, Sho Hangai, Keiko Endo, Sanae Ashitani, Maki Sugaya, Tsuyoshi Osawa, Tomoyoshi Soga, Tadatsugu Taniguchi, Hideyuki Yanai
Summary: Ectopic expression of inhibitory immune ligands by tumors can escape immune destruction, and spermidine, an oncometabolite, has been identified as an inhibitor of T cell receptor signaling. The use of polyamine synthesis inhibitors enhances CD8+ T cell-dependent antitumor responses and combining it with anti-PD-1 immune checkpoint antibody results in a stronger antitumor immune response.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biotechnology & Applied Microbiology
Stefan A. Schattgen, Kate Guion, Jeremy Chase Crawford, Aisha Souquette, Alvaro Martinez Barrio, Michael J. T. Stubbington, Paul G. Thomas, Philip Bradley
Summary: Integrating T cell sequences and gene expression profiles uncovers functional subsets in single-cell datasets, revealing relationships between TCR sequences and phenotypes. The CoNGA approach identifies correlations between TCR sequence and GEX profiles through statistical analysis, helping elucidate complex relationships in large single-cell datasets.
NATURE BIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ahmed S. Fahad, Cheng-Yu Chung, Sheila N. Lopez Acevedo, Nicoleen Boyle, Bharat Madan, Matias F. Gutierrez-Gonzalez, Rodrigo Matus-Nicodemos, Amy D. Laflin, Rukmini R. Ladi, John Zhou, Jacy Wolfe, Sian Llewellyn-Lacey, Richard A. Koup, Daniel C. Douek, Henry H. Balfour, David A. Price, Brandon J. DeKosky
Summary: This study developed a new high-throughput approach for functional evaluation of TCRs. By leveraging physically linked TCR libraries, it enabled repertoire-scale analysis of TCR binding to multiple pMHCs. Affinity-based functional mapping in conjunction with next-generation sequencing was used to track antigen-specific TCRs.
PROTEIN ENGINEERING DESIGN & SELECTION
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
John Miles, Thomas Watkins, Sam Darko, Kuatrinnus Wijaya, Martha Cooper, Amy Ransier, Ashley Waardenberg, Fiona Amante, James Mccarthy, David Price, Scott Burrows
Article
Gastroenterology & Hepatology
Janine Kemming, Swantje Gundlach, Marcus Panning, Daniela Huzly, Jiabin Huang, Marc Luetgehetmann, Sven Pischke, Julian Schulze Zur Wiesch, Florian Emmerich, Sian Llewellyn-Lacey, David A. Price, Yakup Tanriver, Klaus Warnatz, Tobias Boettler, Robert Thimme, Maike Hofmann, Nicole Fischer, Christoph Neumann-Haefelin
Summary: Chronic HEV infection is associated with exhaustion of HEV-specific CD8+ T cells, indicating that T-cell failure is driven by persistent antigen recognition in severely immunosuppressed hosts. Functional reinvigoration of virus-specific T cells is at least partially possible when the antigen is cleared. Viral escape in a minority of patients also contributes to the failure of HEV-specific CD8+ T cells.
JOURNAL OF HEPATOLOGY
(2022)
Article
Cell Biology
Phillip Pymm, Stefan Tenzer, Edmund Wee, Mirjana Weimershaus, Anne Burgevin, Simon Kollnberger, Jan Gerstoft, Tracy M. Josephs, Kristin Ladell, James E. McLaren, Victor Appay, David A. Price, Lars Fugger, John I. Bell, Hansjoerg Schild, Peter van Endert, Maria Harkiolaki, Astrid K. N. Iversen
Summary: This study discovers that the cytotoxic T lymphocyte (CTL) and natural killer (NK) cell responses to a specific epitope in the human immunodeficiency virus are associated with enhanced immune control. The length and mutations of the epitope influence the CTL and NK cell responses, leading to viral escape.
Letter
Biochemical Research Methods
Mikhail Goncharov, Dmitry Bagaev, Dmitrii Shcherbinin, Ivan Zvyagin, Dmitry Bolotin, Paul G. Thomas, Anastasia A. Minervina, Mikhail V. Pogorelyy, Kristin Ladell, James E. McLaren, David A. Price, Thi H. O. Nguyen, Louise C. Rowntree, E. Bridie Clemens, Katherine Kedzierska, Garry Dolton, Cristina Rafael Rius, Andrew Sewell, Jerome Samir, Fabio Luciani, Ksenia V. Zornikova, Alexandra A. Khmelevskaya, Saveliy A. Sheetikov, Grigory A. Efimov, Dmitry Chudakov, Mikhail Shugay
Article
Immunology
Timothy A. A. Gondre-Lewis, Chao Jiang, Mandy L. Ford, David M. Koelle, Alessandro Sette, Alex K. Shalek, Paul G. Thomas
Summary: On June 15-16, 2022, the National Institute of Allergy and Infectious Diseases organized a virtual workshop to discuss T cell technologies including assays, development of novel technologies, their applications in both laboratory and clinical settings, as well as the challenges and innovations in the field.
Article
Immunology
Davide Proietto, Beatrice Dallan, Eleonora Gallerani, Valentina Albanese, Sian Llewellyn-Lacey, David A. Price, Victor Appay, Salvatore Pacifico, Antonella Caputo, Francesco Nicoli, Riccardo Gavioli
Summary: Age-related changes in the immune system affect the ability of elderly individuals to generate effective CD8(+) T cell responses against SARS-CoV-2. Elderly individuals show a deficit in priming naive precursors into effector CD8(+) T cells, resulting in reduced diversity and expression frequency of IFN-gamma in CD8(+) T cell responses. These findings have implications for developing strategies to protect the elderly against COVID-19.
Article
Biology
Freya R. R. Shepherd, Kate Davies, Kelly L. L. Miners, Sian Llewellyn-Lacey, Simon Kollnberger, James E. E. Redman, Melissa M. M. Grant, Kristin Ladell, David A. A. Price, James E. E. McLaren
Summary: Severe bacterial or viral infections can lead to an overactive immune response known as a cytokine storm. Superantigens are potent toxins that activate T cells non-specifically, leading to T cell dysfunction and immune evasion. This study found that TRBV12-3/12-4(+) T cells are highly responsive to streptococcal pyrogenic exotoxin C (SpeC) and toxic shock syndrome toxin-1 (TSST-1).
COMMUNICATIONS BIOLOGY
(2023)
Article
Immunology
Lisa Ciacchi, Martijn D. B. van de Garde, Kristin Ladell, Carine Farenc, Martien C. M. Poelen, Kelly L. Miners, Carmen Llerena, Hugh H. Reid, Jan Petersen, David A. Price, Jamie Rossjohn, Cecile A. C. M. van Els
Summary: A new research found that the immune responses against Streptococcus pneumoniae are mediated by CD4+ T cells. The study identified an immunodominant CD4+ T cell epitope from pneumolysin, which can be presented by different HLA allotypes and recognized by diverse TCRs. The immunogenicity of this epitope is determined by core residues in a conserved undecapeptide region, enabling cross-recognition of heterologous bacterial pathogens. These findings provide insights into the immune response against bacterial infections and can inform strategies to combat life-threatening infectious diseases.
Review
Immunology
Marcus Buggert, David A. Price, Laura K. Mackay, Michael R. Betts
Summary: Our current understanding of human memory CD8(+) T cells mainly comes from studies of the intravascular space, but new data challenges some established ideas and suggests the need for conceptual revision. This review provides a brief history of the field and summarizes the biology of circulating and tissue-resident memory CD8(+) T cells, which play a crucial role in immune surveillance. The authors also discuss how future human studies can improve our understanding of CD8(+) T cells and inform the development of better immunotherapies and vaccines.
Article
Virology
Sherri L. L. Surman, Bart G. G. Jones, Rhiannon R. R. Penkert, Robert E. E. Sealy, Tony Marion, Paul G. G. Thomas, Geoffrey Neale, Beisi Xu, Julia L. L. Hurwitz
Summary: Females generally have stronger immune responses compared to males, which may be attributed to higher estrogen levels. Experiments on animals and humans have shown that supplementation of estrogen can improve immune responses. These findings are important for the optimization of vaccines and drugs for both male and female hosts.
Correction
Immunology
Marcus Buggert, David A. Price, Laura K. Mackay, Michael R. Betts
Review
Medicine, Research & Experimental
Mohamed A. Ghonim, David F. Boyd, Tim Flerlage, Paul G. Thomas
Summary: In recent years, the role of fibroblasts in inflammation has attracted increasing interest. Fibroblasts exhibit diverse functionality and subsets, with phenotypes that depend on their spatial distribution within tissues and immunopathologic cues. In addition to their structural support and tissue remodeling roles, fibroblasts mediate crucial interactions with immune cells, which have significant implications for disease mechanisms and therapeutic targets. Fibroblasts in the respiratory tract play a pivotal role in determining the severity and outcome of various acute and chronic lung diseases.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Cell Biology
Mikhail V. Pogorelyy, Elisa Rosati, Anastasia A. Minervina, Robert C. Mettelman, Alexander Scheffold, Andre Franke, Petra Bacher, Paul G. Thomas
Summary: This study conducted a meta-analysis of large, publicly available TCR datasets from SARS-CoV-2-infected individuals to identify public CD4(+) responses. The results revealed over 1,200 abTCRs forming six prominent similarity clusters, and the validation of HLA restriction and epitope specificity predictions for five clusters using transgenic T cell lines. Overall, these findings provide insights into immunodominant CD4(+) T cell responses to SARS-CoV-2 and demonstrate the utility of the reverse epitope discovery approach.
CELL REPORTS MEDICINE
(2022)