Review
Immunology
Curtis J. Pritzl, Mark A. Daniels, Emma Teixeiro
Summary: CD8 positive, tissue resident memory T cells are a specialized subset of T cells that provide critical protection against tumors and pathogen re-infection. The development and maintenance of these cells involve a myriad of signals, including tissue-derived signals and antigenic/pro-inflammatory cytokines. Recent research suggests additional roles for antigenic and pro-inflammatory signals in the establishment of resident memory T cells.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Hongling Huang, Peipei Zhou, Jun Wei, Lingyun Long, Hao Shi, Yogesh Dhungana, Nicole M. Chapman, Guotong Fu, Jordy Saravia, Jana L. Raynor, Shaofeng Liu, Gustavo Palacios, Yong-Dong Wang, Chenxi Qian, Jiyang Yu, Hongbo Chi
Summary: This study reveals that amino acid transporters play a role in dampening T-MEM differentiation, while Pofut1 is a key regulator for terminal effector differentiation of T-EFF cells. These findings highlight the importance of nutrient uptake and signaling in determining T cell fate.
Article
Cell Biology
Florian Schmidt, Hannah F. Fields, Yovita Purwanti, Ana Milojkovic, Syazwani Salim, Kan Xing Wu, Yannick Simoni, Antonella Vitiello, Daniel T. Macleod, Alessandra Nardin, Evan W. Newell, Katja Fink, Andreas Wilm, Michael Fehlings
Summary: In this study, high-dimensional mass cytometry and single-cell RNA sequencing were used to analyze CD8(+) T cells binding to different virus antigens. Phenotypic signatures of antigen-specific T cells were extracted using machine learning, which accurately predicted virus specificity for bulk CD8(+) T cells.
Review
Immunology
Tamar Nizharadze, Nils B. Becker, Thomas Hoefer
Summary: This study uses mathematical inference to establish quantitatively testable models of mammalian CD8+ T cell memory development based on complex experimental data. Previous inference studies have shown that precursors of memory T cells develop early in the immune response. Recent work has validated a crucial prediction of this T cell diversification model and refined the model.
TRENDS IN IMMUNOLOGY
(2023)
Review
Immunology
Gaia Montacchiesi, Luigia Pace
Summary: After antigen recognition, CD8(+) T lymphocytes differentiate into different subsets with distinct phenotypes, functions, and migration properties. Transcription factors and chromatin structure changes drive the functional differentiation and phenotypic diversity of these T cell subsets, which has implications for new immunotherapy protocols and vaccination strategies. Understanding the contribution of chromatin architecture and transcription factor activity in guiding CD8(+) T cell subset commitment is important for T cell plasticity, stability, and memory in infection and cancer.
IMMUNOLOGICAL REVIEWS
(2022)
Review
Immunology
Rut Mora-Buch, Shannon K. Bromley
Summary: Resident memory CD8(+) T cells provide rapid local protection and control tumor growth, but dysregulation may contribute to autoimmune diseases. Intrinsic mechanisms and extrinsic stimuli regulate T-RM differentiation and response.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Allergy
Komal Agrawal, Li Ching Ong, Susan Monkley, Kristofer Thorn, Elisabeth Israelsson, Engin Baturcam, Cassie Rist, Karin Schon, Sophia Blake, Bjorn Magnusson, James Cartwright, Suman Mitra, Abilash Ravi, Nazanin Zounemat-Kermani, Jayendra Kumar Krishnaswamy, Nils Y. Lycke, Ulf Gehrmann, Johan Mattsson
Summary: Patients with asthma experience reduced ability to clear respiratory viral infections due to changes in gene expression in nasal and lung epithelial cells. These changes interfere with the development of lung resident memory T cells, which may contribute to the increased susceptibility of patients with asthma to viral exacerbations.
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Andrea Papait, Elsa Vertua, Patrizia Bonassi Signoroni, Anna Cargnoni, Marta Magatti, Francesca Romana Stefani, Jacopo Romoli, Antonietta Rosa Silini, Ornella Parolini
Summary: We found that hAMSCs from human term placenta can affect the development and fate of CD8 T cells through multiple mechanisms, providing new insights into the treatment of diseases characterized by altered activation of memory subsets.
Article
Multidisciplinary Sciences
Sarah Adamo, Jan Michler, Yves Zurbuchen, Carlo Cervia, Patrick Taeschler, Miro E. Raeber, Simona Baghai Sain, Jakob Nilsson, Andreas E. Moor, Onur Boyman
Summary: Researchers used spectral flow cytometry combined with cellular indexing of transcriptomes and T cell receptor sequencing to longitudinally characterize individual SARS-CoV-2-specific CD8(+) T cells from patients with COVID-19, identifying a distinct signature marking long-lived memory CD8(+) T cells. The study found that SARS-CoV-2-specific memory CD8(+) T cells persisting 1 year after acute infection express specific markers and exhibit characteristics resembling effector memory T cells, and that certain transcriptional signatures and signaling pathways are associated with the fate of individual clones of these cells.
Article
Multidisciplinary Sciences
Mladen Jergovic, Christopher P. Coplen, Jennifer L. Uhrlaub, David G. Besselsen, Shu Cheng, Megan J. Smithey, Janko Nikolich-Zugich
Summary: Infections can lead to the expansion of a subpopulation of long-lived, Ly6C(+) CD8(+) Tn cells with accelerated effector function, depending on the action of IFN-I. This highlights the significant role of infection-driven IFN-I in regulating Tn homeostasis and function, with potential implications for immunotherapy.
NATURE COMMUNICATIONS
(2021)
Review
Immunology
Mohammad Heidarian, Thomas S. S. Griffith, Vladimir P. P. Badovinac
Summary: Formation of long-lasting memory lymphocytes is crucial for adaptive immunity and vaccination strategies. Memory CD8 T cells, which are distinct from naive CD8 T cells, display heterogeneity in tissue localization, cytotoxic ability, and proliferative capacity. Sepsis not only reduces the number and function of memory CD8 T cells, but also alters their transcriptional profile and impairs their protective capacity. This review explores different aspects of memory CD8 T cell subsets and the impact of sepsis on their biology.
FRONTIERS IN IMMUNOLOGY
(2023)
Editorial Material
Immunology
Tiani L. Louis, John T. Chang
Summary: In this study, Hirai et al. demonstrate the competition for the cytokine TGF beta as a key factor in regulating the persistence and occupancy of CD8(+) tissue-resident memory T cells in the skin epidermal niche.
Article
Multidisciplinary Sciences
Nadine Kamenjarin, Katrin Hodapp, Felix Melchior, Gregory Harms, Ann- Kathrin Hartmann, Joschka Bartneck, Sabine Muth, Verena K. Raker, Christian Becker, Anna Brand, Bjorn E. Clausen, Markus P. Radsak, Hansjorg Schild, Hans Christian Probst
Summary: Tissue-resident memory CD8+ T cells (TRM) in the skin require epidermal Langerhans cells, which cross-present keratinocyte-derived antigens, for their reactivation to provide protection against reinfection.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biology
Isaac J. Jensen, Xiang Li, Patrick W. McGonagill, Qiang Shan, Micaela G. Fosdick, Mikaela M. Tremblay, Jon Cd Houtman, Hai-Hui Xue, Thomas S. Griffith, Weiqun Peng, Vladimir P. Badovinac
Summary: The study found that sepsis leads to a reduction in memory CD8 T cells, but surviving cells proliferate quickly, especially a subpopulation called central memory CD8 T cells, thereby changing the overall composition of the memory CD8 T cell pool. This increased proliferation results in long-term changes in the quantity and composition of immune cells, potentially affecting the host's ability to respond to re-infection.
Article
Multidisciplinary Sciences
Ao Guo, Hongling Huang, Zhexin Zhu, Mark J. Chen, Hao Shi, Sujing Yuan, Piyush Sharma, Jon P. Connelly, Swantje Liedmann, Yogesh Dhungana, Zhenrui Li, Dalia Haydar, Mao Yang, Helen Beere, Jason T. Yustein, Christopher DeRenzo, Shondra M. Pruett-Miller, Jeremy Chase Crawford, Giedre Krenciute, Charles W. M. Roberts, Hongbo Chi, Douglas R. Green
Summary: This study identifies components of the cBAF complex as negative regulators of T-mem cell generation and provides insights into the asymmetric distribution of cBAF and MYC during the division of activated CD8+ T cells. Manipulation of cBAF early in T cell differentiation has the potential to improve cancer immunotherapy, as demonstrated in a mouse solid tumor model.
Article
Immunology
Deborah Cromer, Arnold Reynaldi, Megan Steain, James A. Triccas, Miles P. Davenport, David S. Khoury
Summary: The vaccine candidate CVnCoV (CUREVAC) exhibited lower efficacy compared to other mRNA vaccines in a recent phase 3 trial, which can be attributed to the dosage used and the presence of SARS-CoV-2 variants. The neutralizing antibody response induced by the vaccine can predict the low efficacy.
CLINICAL INFECTIOUS DISEASES
(2022)
Article
Immunology
Jillian S. Y. Lau, Deborah Cromer, Mykola Pinkevych, Sharon R. Lewin, Thomas A. Rasmussen, James H. McMahon, Miles P. Davenport
Summary: This study used mathematical models to explore ways to improve ATI study design to maximize statistical power and minimize risks to participants.
JOURNAL OF INFECTIOUS DISEASES
(2022)
Article
Infectious Diseases
Arya SheelaNair, Aleksandra S. Romanczuk, Rosemary A. Aogo, Rohit Nemai Haldar, Lianne I. M. Lansink, Deborah Cromer, Yandira G. Salinas, R. Kiplin Guy, James S. McCarthy, Miles P. Davenport, Ashraful Haque, David S. Khoury
Summary: This study compared the effects of different anti-malarial drugs on mice infected with malaria. The results showed that different drugs varied in their ability to reduce parasite count and had different mechanisms of action. This suggests that although the parasite clearance curves may be similar, the drugs have different capacities to inhibit, kill, and clear parasites.
Article
Multidisciplinary Sciences
Sandile Cele, Laurelle Jackson, David S. Khoury, Khadija Khan, Thandeka Moyo-Gwete, Houriiyah Tegally, James Emmanuel San, Deborah Cromer, Cathrine Scheepers, Daniel G. Amoako, Farina Karim, Mallory Bernstein, Gila Lustig, Derseree Archary, Muneerah Smith, Yashica Ganga, Zesuliwe Jule, Kajal Reedoy, Shi-Hsia Hwa, Jennifer Giandhari, Jonathan M. Blackburn, Bernadett Gosnell, Salim S. Abdool Karim, Willem Hanekom, Anne von Gottberg, Jinal N. Bhiman, Richard J. Lessells, Mahomed-Yunus S. Moosa, Miles P. Davenport, Tulio de Oliveira, Penny L. Moore, Alex Sigal
Summary: The study found that the Omicron variant has reduced neutralizing effectiveness in individuals vaccinated with Pfizer BNT162b2, but those who had previously been infected with SARS-CoV-2 showed better neutralization against Omicron.
Article
Immunology
Yongyao Fu, Jocelyn Wang, Baohua Zhou, Abigail Pajulas, Hongyu Gao, Baskar Ramdas, Byunghee Koh, Benjamin J. Ulrich, Shuangshuang Yang, Reuben Kapur, Jean-Christophe Renauld, Sophie Paczesny, Yunlong Liu, Robert M. Tighe, Paula Licona-Limon, Richard A. Flavell, Shogo Takatsuka, Daisuke Kitamura, Robert S. Tepper, Jie Sun, Mark H. Kaplan
Summary: This study reveals that IL-9 mediates proallergic activities in the lungs by targeting lung macrophages. Interstitial macrophages are required for IL-9-dependent allergic responses. Mechanistically, IL-9 affects the function of lung macrophages by inducing Arg1 activity.
SCIENCE IMMUNOLOGY
(2022)
Article
Dermatology
Jocelyn Wang, Abigail Pajulas, Yongyao Fu, Djamilatou Adom, Wenwu Zhang, Andrew S. Nelson, Dan F. Spandau, Mark H. Kaplan
Summary: Atopic dermatitis leads to changes in skin function, including barrier impairment and altered production of antimicrobial peptides. This study found that allergic skin inflammation results in a significant decrease in a specific population of T cells in the skin, which is dependent on IL-4. Furthermore, it was observed that wound healing process is hindered in allergic skin inflammation, but can be rescued by cytokines produced by specific T cells.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2022)
Article
Immunology
Kathleen M. Wragg, Wen Shi Lee, Marios Koutsakos, Hyon-Xhi Tan, Thakshila Amarasena, Arnold Reynaldi, Grace Gare, Penny Konstandopoulos, Kirsty R. Field, Robyn Esterbauer, Helen E. Kent, Miles P. Davenport, Adam K. Wheatley, Stephen J. Kent, Jennifer A. Juno
Summary: Wragg and colleagues tracked clonal populations of spike-specific CD4(+) cT(FH) cells using MHC class II tetramers and TCR beta sequencing in convalescent individuals with COVID-19 or SARS-CoV-2-vaccinated individuals. They found that both infection and vaccination induced CD4(+) T cell responses to the spike protein and that these responses correlated with neutralizing antibodies. Secondary exposure led to the recall of CD4(+) T cells with a transitory CXCR3(+) phenotype and expansion of cT(FH) cells temporarily expressing ICOS, CD38, and PD-1. The study demonstrates that stable pools of cT(FH) and memory CD4(+) T cells established by infection and/or vaccination can be efficiently recalled and may contribute to long-term protection against SARS-CoV-2.
Article
Multidisciplinary Sciences
Yongyao Fu, Abigail Pajulas, Jocelyn Wang, Baohua Zhou, Anthony Cannon, Cherry Cheuk Lam Cheung, Jilu Zhang, Huaxin Zhou, Amanda Jo Fisher, David T. Omstead, Sabrina Khan, Lei Han, Jean-Christophe Renauld, Sophie Paczesny, Hongyu Gao, Yunlong Liu, Lei Yang, Robert M. Tighe, Paula Licona-Limon, Richard A. Flavell, Shogo Takatsuka, Daisuke Kitamura, Jie Sun, Basar Bilgicer, Catherine R. Sears, Kai Yang, Mark H. Kaplan
Summary: The role of IL-9 in the tumor microenvironment and its effects on macrophages have been investigated. The study shows that IL-9 promotes the expansion of pulmonary macrophages and targeting the IL-9R/arginase 1 axis restricts tumor growth, suggesting that this cytokine pathway could be a potential therapeutic target for lung cancer.
NATURE COMMUNICATIONS
(2022)
Editorial Material
Cell Biology
Hyon-Xhi Tan, Miles P. Davenport, Stephen J. Kent, Adam K. Wheatley
IMMUNOLOGY AND CELL BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Cybelle Tabilas, David S. Iu, Ciaran W. P. Daly, Kristel J. Yee Mon, Arnold Reynaldi, Samantha P. Wesnak, Jennifer K. Grenier, Miles P. Davenport, Norah L. Smith, Andrew Grimson, Brian D. Rudd
Summary: Microbial exposure during development can have long-lasting effects on an individual's health, but how early microbial exposure leads to permanent changes in the immune system is still unclear. This study shows that early microbial exposure results in the preferential expansion of specific CD8+ T cell populations, which persist and provide enhanced immune protection against intracellular pathogens. Interestingly, this microbial education occurs during thymic development and involves changes in epigenetic programming.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
David S. Khoury, Steffen S. Docken, Kanta Subbarao, Stephen J. Kent, Miles P. Davenport, Deborah Cromer
Summary: Booster vaccination is necessary to combat waning immunity and variants of SARS-CoV-2. Data on neutralization titers from multiple sources suggest that using ancestral vaccines can enhance protection against symptomatic and severe disease caused by variant viruses. Variant-modified vaccines may provide additional benefits. This study provides evidence-based guidance for future COVID-19 vaccine regimens.
Article
Multidisciplinary Sciences
Deborah Cromer, Megan Steain, Arnold Reynaldi, Timothy E. Schlub, Shanchita R. Khan, Sarah C. Sasson, Stephen J. Kent, David S. Khoury, Miles P. Davenport
Summary: The study demonstrates a strong correlation between neutralising antibody titres and vaccine effectiveness against symptomatic and severe COVID-19. Predicted neutralising antibody titres are strongly correlated with observed vaccine effectiveness, and the loss of neutralising antibodies over time and to new variants is predictive of observed vaccine protection against severe COVID-19.
NATURE COMMUNICATIONS
(2023)
Article
Immunology
Stephen J. Kent, David S. Khoury, Arnold Reynold, Jennifer A. Juno, Adam K. Wheatley, Eva Stadler, E. John Wherry, James Triccas, Sarah C. Sasson, Deborah Cromer, Miles P. Davenport
Summary: Understanding the role of T cells in SARS-CoV-2 infection is crucial for the design of next-generation vaccines. This perspective discusses the challenges in determining the causal relationship between vaccine-induced T cell immunity and protection from COVID-19, and proposes an approach to gather evidence and clarify the role of vaccine-induced T cell memory in protecting against severe COVID-19.
NATURE REVIEWS IMMUNOLOGY
(2022)
Article
Immunology
Maria Rebelo, Rebecca Pawliw, Jeremy Gower, Lachlan Webb, Hayley Mitchell, Zuleima Pava, Rebecca E. Watts, Miles P. Davenport, James S. McCarthy, David S. Khoury
Summary: This study found that viable parasites in artemisinin-sensitive infections decreased to <0.1% of baseline within 8 hours after artesunate administration, while the total number of circulating parasites measured with quantitative polymerase chain reaction remained unchanged. In artemisinin-resistant infections over the same interval, viable parasites declined to 51.4% of baseline. These results suggest that the in vivo drug activity of artesunate is quicker than previously reported based on parasite clearance half-life.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Review
Immunology
Deborah Cromer, Jennifer A. Juno, David Khoury, Arnold Reynaldi, Adam K. Wheatley, Stephen J. Kent, Miles P. Davenport
Summary: The duration of immunity to COVID-19 and the risk of reinfection remain unclear. Immunity is crucial for long-term control of the pandemic, but studies suggest a decline in antibody responses and an increase in documented cases of reinfection with SARS-CoV-2. Understanding memory responses and immune control dynamics is essential for designing vaccines and predicting the future trajectory of the pandemic.
NATURE REVIEWS IMMUNOLOGY
(2021)