Article
Immunology
Duncan C. Humphries, Richard A. O'Connor, Hazel L. Stewart, Tom M. Quinn, Erin E. Gaughan, Beth Mills, Gareth O. S. Williams, James M. Stone, Keith Finlayson, Martine Chabaud-Riou, Florence Boudet, Kevin Dhaliwal, Vincent Pavot
Summary: This study developed a novel method combining ex vivo lung ventilation and fibre-based optical endomicroscopy to detect in situ lymphocyte tissue residency markers in human lungs. This method has significant implications for both research and clinical applications.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Marco Kunzli, David Masopust
Summary: This review provides updates on our understanding of the biology of memory CD4(+) T cells as well as key technological advances that facilitate their characterization.
Article
Multidisciplinary Sciences
Ariel Isser, Aliyah B. Silver, Hawley C. Pruitt, Michal Mass, Emma H. Elias, Gohta Aihara, Si-Sim Kang, Niklas Bachmann, Ying-Yu Chen, Elissa K. Leonard, Joan G. Bieler, Worarat Chaisawangwong, Joseph Choy, Sydney R. Shannon, Sharon Gerecht, Jeffrey S. Weber, Jamie B. Spangler, Jonathan P. Schneck
Summary: ACT using artificial antigen-presenting cells can expand both CD4(+) and CD8(+) T cells, showing potential therapeutic efficacy in cancer treatment.
NATURE COMMUNICATIONS
(2022)
Article
Biology
Marie Strickland, Salanne Lee, Shi Yong Neo, Akhila Balachander, Ivy Low, Seri Mustafah, Wah Ing Goh, Graham D. D. Wright, Anis Larbi, Sylvia L. F. Pender
Summary: The study focuses on investigating the impact of mitochondrial dysfunction on immune responses to infection and vaccination in the elderly population. Specifically, it examines the metabolic responses and mitochondrial dynamics of CD4+ TEMRA cells and other CD4+ memory T cell subtypes. The results show that CD4+ TEMRA cells exhibit altered mitochondrial dynamics, increased glucose uptake, and higher mitochondrial mass, which may contribute to impaired responses to infection and vaccination.
Article
Cell Biology
Jake C. Harbour, Mahmoud Abdelbary, John B. Schell, Samantha P. Fancher, Jack J. McLean, Taylen J. Nappi, Susan Liu, Timothy J. Nice, Zheng Xia, Klaus Fruh, Jeffrey C. Nolz
Summary: This study found that Th1 memory CD4+ T cells are crucial for protecting against poxvirus skin infections, while CD8+ T cells are not necessary. Th1 effector memory CD4+ T cells rapidly infiltrate the poxvirus-infected skin microenvironment and produce interferon γ to promote anti-viral immunity. Keratinocytes are the key targets of IFNγ necessary for preventing poxvirus infection of the epidermis.
Article
Immunology
Sarah L. Bevington, Remi Fiancette, Dominika W. Gajdasik, Peter Keane, Jake K. Soley, Claire M. Willis, Daniel J. L. Coleman, David R. Withers, Peter N. Cockerill
Summary: Research reveals that T cell immunological memory is established within 7 days post-infection, with epigenetic programs playing a crucial role in Th differentiation and memory T cell formation. Memory T cell-specific regulatory elements contribute to enhanced inducible responses during secondary antigen exposures.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Benedikt Thelen, Vincent Schipperges, Paulina Knoerlein, Jonas F. Hummel, Frederic Arnold, Laurence Kupferschmid, Christoph S. N. Klose, Sebastian J. Arnold, Melanie Boerries, Yakup Tanriver
Summary: T-bet and Eomesodermin are T-box transcription factors that regulate type 1 immune responses in innate and adaptive lymphocytes. T-bet is the lineage-specifying transcription factor of Th1 CD4(+) T cells and controls the expression of IFN-gamma, while Eomes is less abundantly expressed and is found in CD4(+) T cells exposed to chronic antigen stimulation. A new genetic approach showed that Eomes drives a distinct transcriptional program in CD4(+) T cells that only partially overlaps with T-bet. Eomes(+) CD4(+) T cells induce the expression of IL-10 and promote a cytotoxic effector profile, suggesting that they are a unique CD4(+) T cell subset that limits inflammation and eliminates antigen-presenting and malignant cells.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cell Biology
Susan L. Swain, Michael C. Jones, Priyadharshini Devarajan, Jingya Xia, Richard W. Dutton, Tara M. Strutt, K. Kai McKinstry
Summary: The fate of CD4 effector and memory cells after infection is influenced by initial signals as well as a second round of signals during the effector response. Effective vaccine strategies should aim to provide extended signals from antigen and pathogen to induce more effective and durable immunity. Understanding the mechanisms that underlie effective immune responses is crucial for the development of such strategies.
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
(2021)
Article
Immunology
Rashmi Tippalagama, Akul Singhania, Paige Dubelko, Cecilia S. Lindestam Arlehamn, Austin Crinklaw, Mikhail Pomaznoy, Gregory Seumois, Aruna D. DeSilva, Sunil Premawansa, Dhammika Vidanagama, Bandu Gunasena, N. D. Suraj Goonawardhana, Dinuka Ariyaratne, Thomas J. Scriba, Robert H. Gilman, Mayuko Saito, Randy Taplitz, Pandurangan Vijayanand, Alessandro Sette, Bjoern Peters, Julie G. Burel
Summary: This study investigated the molecular profile of CD4 T cells in individuals with active tuberculosis, finding that HLA-DR can serve as a marker for recently expanded antigen-specific CD4 T cells.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Immunology
Carolina Lyon De Ana, Anukul T. Shenoy, Kimberly A. Barker, Emad I. Arafa, Neelou S. Etesami, Filiz T. Korkmaz, Alicia M. Soucy, Michael P. Breen, Ian M. C. Martin, Brian R. Tilton, Priyadharshini Devarajan, Nicholas A. Crossland, Riley M. F. Pihl, Wesley N. Goltry, Anna C. Belkina, Matthew R. Jones, Lee J. Quinton, Joseph P. Mizgerd
Summary: Streptococcus pneumoniae is a common bacterial pathogen that causes pneumonia, leading to significant mortality in children and the elderly worldwide. This study identifies a unique subset of CD4+ TRM cells in the lungs that play a crucial role in lung immunity during pneumococcal infections. These cells exhibit distinct functional characteristics compared to other subsets, suggesting their importance in protecting against reinfection.
MUCOSAL IMMUNOLOGY
(2023)
Article
Immunology
Quynh P. Nguyen, Kennidy K. Takehara, Tianda Z. Deng, Shannon O'Shea, Maximilian Heeg, Kyla D. Omilusik, J. Justin Milner, Sara Quon, Matthew E. Pipkin, Jinyong Choi, Shane Crotty, Ananda W. Goldrath
Summary: After infection, T cells differentiate into long-lived memory cells that can circulate through secondary lymphoid organs or reside in tissues. CD4+ tissue-resident memory T cells (TRM) in the small intestine (SI) responding to acute viral infection share a gene expression program and chromatin accessibility profile with circulating TH1 cells, and gradually acquire a mature TRM program. Single-cell RNA sequencing reveals heterogeneity among established CD4+ TRM, predominantly located in the lamina propria, and identifies a population of cells that coexpress both effector- and memory-associated genes. Transcriptional regulators Blimp1, Id2, and Bcl6 are required for the formation and development of CD4+ TRM in the SI. These findings provide insights into the development, differentiation, and persistence of CD4+ TRM in response to viral infection.
SCIENCE IMMUNOLOGY
(2023)
Article
Cell Biology
Yu-Jung Lu, Palmira Barreira-Silva, Shayla Boyce, Jennifer Powers, Kelly Cavallo, Samuel M. Behar
Summary: CD4 T cells play a crucial role in immunity to tuberculosis by enhancing CD8 effector functions and preventing exhaustion, promoting the survival of infected mice. Vaccines that elicit both CD4 and CD8 T cells are more likely to be successful in generating protective responses against M. tuberculosis infection.
Article
Cell Biology
Hiromitsu Asashima, Subhasis Mohanty, Michela Comi, William E. Ruff, Kenneth B. Hoehn, Patrick Wong, Jon Klein, Carolina Lucas, Inessa Cohen, Sarah Coffey, Nikhil Lele, Leissa Greta, Khadir Raddassi, Omkar Chaudhary, Avraham Unterman, Brinda Emu, Steven H. Kleinstein, Ruth R. Montgomery, Akiko Iwasaki, Charles S. Dela Cruz, Naftali Kaminski, Albert C. Shaw, David A. Hafler, Tomokazu S. Sumida
Summary: T cell-B cell interaction is crucial for immune response against severe viral infection, but its role in supporting protective humoral immunity in humans is not well understood. This study investigates CD4+ T cell subsets associated with plasma-blast expansion and clinical outcome in COVID-19 patients. The findings reveal that peripheral helper T cells (Tph cells) are increased and exhibit B cell help signatures, promoting plasmablast differentiation. Expanded plasmablasts express higher levels of CXCR3, positively correlated with activated Tph cells and better clinical outcome. This study uncovers a role for Tph cells in regulating protective B cell response during acute viral infection.
Article
Gastroenterology & Hepatology
Nadine N. Morgan, Lennard W. Duck, Jiongru Wu, Mahmud Rujani, Paul G. Thomes, Charles O. Elson, Peter J. Mannon
Summary: Crohn's disease patients exhibit inflammatory cytokine responses to flagellin antigens in an expanded effector memory CD4 subset that is not present in ulcerative colitis or non-inflammatory bowel disease control subjects. These cells are correlated with levels of specific anti-flagellin antibodies.
INFLAMMATORY BOWEL DISEASES
(2022)
Article
Multidisciplinary Sciences
Georg Petkau, Twm J. Mitchell, Krishnendu Chakraborty, Sarah E. Bell, Vanessa D. Angeli, Louise Matheson, David J. Turner, Alexander Saveliev, Ozge Gizlenci, Fiamma Salerno, Peter D. Katsikis, Martin Turner
Summary: RNA binding proteins ZFP36 and ZFP36L1 limit the rate of differentiation and the potency of activated CD8(+) T cells by directly binding mRNA of transcription factors and cytokines, enforcing dependency on costimulation for full T cell activation and effector differentiation.
NATURE COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Megan E. Schmidt, Steven M. Varga
Article
Immunology
Megan E. Schmidt, Antonius G. P. Oomens, Steven M. Varga
JOURNAL OF IMMUNOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Abigail R. Berkebile, Jennifer A. Bartlett, Mahmoud Abou Alaiwa, Steven M. Varga, Ultan F. Power, Paul B. McCray
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2020)
Editorial Material
Immunology
Steven M. Varga, Andrea J. Sant
FRONTIERS IN IMMUNOLOGY
(2019)
Article
Immunology
Megan E. Schmidt, David K. Meyerholz, Steven M. Varga
MUCOSAL IMMUNOLOGY
(2020)
Review
Immunology
Laura M. Stephens, Steven M. Varga
Article
Immunology
Jorge A. Soto, Laura M. Stephens, Kody A. Waldstein, Gisela Canedo-Marroquin, Steven M. Varga, Alexis M. Kalergis
FRONTIERS IN IMMUNOLOGY
(2020)
Article
Immunology
Laura M. Stephens, Kathleen A. Ross, Kody A. Waldstein, Kevin L. Legge, Jason S. McLellan, Balaji Narasimhan, Steven M. Varga
Summary: The novel RSV vaccine RSVNanoVax showed protective effects against RSV infection in experiments, reducing weight loss and pulmonary dysfunction, with protection lasting at least 6 months. Additionally, the vaccine was able to rapidly clear RSV from the lungs, induce tissue-resident memory T cells, and produce neutralizing antibodies against RSV.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Biology
Scott M. Anthony, Natalija Van Braeckel-Budimir, Steven J. Moioffer, Stephanie van de Wall, Qiang Shan, Rahul Vijay, Ramakrishna Sompallae, Stacey M. Hartwig, Isaac J. Jensen, Steven M. Varga, Noah S. Butler, Hai-Hui Xue, Vladimir P. Badovinac, John T. Harty
Summary: IAV infection generates Trm CD8(+)T cells in mice, while repeated antigen exposure produces 4M CD8(+)T cells with enhanced protective capacity. Enhanced protection by 4M cells is associated with increased expression of granzyme A/B and stable maintenance of CD69(+)CD103(+) 4M CD8(+)T cells, improving control of viral infections in mLN.
Review
Immunology
Laura M. Stephens, Steven M. Varga
Summary: RSV is commonly associated with acute lower respiratory tract infections in infants and children, but also causes high disease burden in the elderly; RSV infection in aged individuals results in more severe disease symptoms, leading to higher hospitalizations and deaths in the elderly; Developing an RSV vaccine for elderly populations is challenging due to age-related defects in the immune system, but remains an important target for public health prevention strategies.
Article
Immunology
Stacey M. Hartwig, Ann M. Miller, Steven M. Varga
Summary: Respiratory infections are a significant cause of illness and death, and the order in which viral infections are acquired plays a critical role in disease severity and the host immune response. In a study involving mice, it was found that being infected with respiratory syncytial virus (RSV) before influenza A virus (IAV) led to reduced weight loss and increased survival compared to being infected with IAV alone.
JOURNAL OF IMMUNOLOGY
(2022)
Article
Virology
Laura M. Stephens, Kathleen A. Ross, Jason S. McLellan, Balaji Narasimhan, Steven M. Varga
Summary: RSV infection causes significant infections and deaths in children and elderly adults each year. There is currently no licensed vaccine for RSV prevention. This study developed a vaccine candidate, RSVNanoVax, which provided long-term protection and immunity in outbred Swiss Webster mice.
JOURNAL OF VIROLOGY
(2022)
Article
Biochemical Research Methods
Kody A. Waldstein, Jirong Yi, Michael Myung Cho, Raghu Mudumbai, Xiaodong Wu, Steven M. Varga, Weiyu Xu
Summary: The rapid spread of SARS-CoV-2 has highlighted the need for innovative testing approaches for future pandemics. In this study, a novel sample pooling procedure based on compressed sensing theory is presented, which accurately identifies virally infected patients at high prevalence rates. The method reduces the number of tests required and provides quantification of individual sample viral load within a pool.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Microbiology
Kody A. Waldstein, Steven M. Varga
Review
Virology
Laura M. Stephens, Steven M. Varga