Article
Cell Biology
Wenqiang Cao, Ines Sturmlechner, Huimin Zhang, Jun Jin, Bin Hu, Rohit R. Jadhav, Fengqin Fang, Cornelia M. Weyand, Jorg J. Goronzy
Summary: Naive CD4+ T cells are more resistant to age-related loss than naive CD8+ T cells, indicating the presence of mechanisms that preferentially protect naive CD4+ T cells during aging. The study reveals that TRIB2 is more abundant in naive CD4+ T cells and suppresses AKT activation to prevent quiescence exit. Loss of TRIB2 leads to increased AKT activity, accelerated proliferation, and differentiation in response to IL-7. Transcription of TRIB2 is controlled by lineage-determining transcription factors ThPOK and RUNX3. Deletion of Zbtb7b (encoding ThPOK) and Cbfb (obligatory RUNT cofactor) attenuates the difference in lymphopenia-induced proliferation between naive CD4+ and CD8+ cells. In older adults, decreased expression of ThPOK and TRIB2 in naive CD4+ T cells causes loss of naivety. These findings highlight the importance of TRIB2 in regulating T cell homeostasis and provide insights into the differential resilience of CD8+ T cells to age-related changes.
Review
Cell Biology
David A. Lewis, Tony Ly
Summary: CD8(+) T cells are crucial in immunity and immuno-oncology, as they undergo complex cellular growth, cell cycle entry, and differentiation to produce antigen-specific cytotoxic T lymphocytes. Some activated T cells will differentiate into memory T cells which are essential in adaptive immunity. This review explores the control of cell cycle entry in CD8(+) T cells and the interaction between these mechanisms and pathways regulating immunological phenotypes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Mariana Borsa, Niculo Barandun, Fabienne Graebnitz, Isabel Barnstorf, Nicolas S. Baumann, Katharina Pallmer, Samira Baumann, Dominique Stark, Miroslav Balaz, Nathalie Oetiker, Franziska Wagen, Christian Wolfrum, Anna Katharina Simon, Nicole Joller, Yves Barral, Roman Spoerri, Annette Oxenius
Summary: Impaired asymmetric cell division in CD8(+) T cells during aging can be rescued by transient mTOR inhibition, restoring expansion and memory potential of cellular progenies. Virtual memory T cells (T-VM cells) in aged individuals display unique proliferation and metabolic profiles, retaining the ability to divide asymmetrically and having increased memory potential.
NATURE COMMUNICATIONS
(2021)
Article
Immunology
Pavel Shelyakin, Ksenia R. Lupyr, Evgeny S. Egorov, Ilya A. Kofiadi, Dmitriy B. Staroverov, Sofya A. Kasatskaya, Valeriia V. Kriukova, Irina A. Shagina, Ekaterina M. Merzlyak, Tatiana O. Nakonechnaya, Elena A. Latysheva, Irina A. Manto, Musa R. Khaitov, Sergey A. Lukyanov, Dmitriy M. Chudakov, Olga Britanova
Summary: The interplay between T- and B-cell compartments during naive, effector and memory T cell maturation is critical for a balanced immune response. Primary B-cell immunodeficiency arising from X-linked agammaglobulinemia (XLA) offers a model to explore B cell impact on T cell subsets, starting from the thymic selection. The findings suggest active B cell involvement in CD4 T cell subsets maturation, including B cell-dependent expansion of the naive Treg TCR repertoire that enables better control of self-reactive T cells.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Melba Munoz, Ahmed N. Hegazy, Tobias M. Brunner, Vivien Holecska, Roman M. Marek, Anja Froehlich, Max Loehning
Summary: Th2 cells lacking T-bet exhibit strong immunomodulatory potential by suppressing antigen-specific CD8(+) T cell responses via IL-10. These cells protect mice against virus-induced type 1 diabetes and hinder effector and cytotoxic CD8(+) T cell development by downregulating dendritic cell activation. IL-10-secreting Th2 cells could potentially be used as a therapeutic approach for T cell-mediated inflammatory disorders.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Marie Bleakley, Alison Sehgal, Stuart Seropian, Melinda A. Biernacki, Elizabeth F. Krakow, Ann Dahlberg, Heather Persinger, Barbara Hilzinger, Paul J. Martin, Paul A. Carpenter, Mary E. Flowers, Jenna Voutsinas, Theodore A. Gooley, Keith Loeb, Brent L. Wood, Shelly Heimfeld, Stanley R. Riddell, Warren D. Shlomchik
Summary: This study evaluated the impact of T-N depletion on chronic GVHD (cGVHD) and other outcomes. The results showed that T-N depletion significantly reduced the incidence of GVHD without increasing the risk of relapse and nonrelapse mortality.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Immunology
Jaekwan Kim, Thomas Nguyen, Jeffrey Cifello, Raheel Ahmad, Yongqing Zhang, Qian Yang, Ji-Eun Lee, Xiang Li, Yan Kai, Supriyo De, Weiqun Peng, Kai Ge, Nan-ping Weng
Summary: Lysine specific methyltransferase 2D (Kmt2d) regulates the generation and survival of regulatory T cells and naive CD8(+) T cells through modulating H3K4me1 modification.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biology
Sanket Rane, Thea Hogan, Edward Lee, Benedict Seddon, Andrew J. Yates
Summary: In this study, a unified model of naive CD4 and CD8 T cell population dynamics in mice was identified using multiple modelling and experimental approaches. It was found that both subsets divide rarely and progressively increase their survival capacity with cell age. Newly generated naive CD8 T cells were found to be lost more rapidly during the first 3-4 weeks of life. No evidence for elevated division rates in neonates or feedback regulation of naive T cell numbers at any age was found.
Article
Oncology
Sandhya Sharma, Mae Woods, Naren U. Mehta, Tim Sauer, Kathan S. Parikh, Michael Schmuck-Henneresse, Huimin Zhang, Birju Mehta, Malcolm K. Brenner, Helen E. Heslop, Cliona M. Rooney
Summary: This study found that depleting naive T cells before extracting antigen-specific T cells from patients can enhance their expansion, antigen specificity, and therapeutic potency. By using CD45RA-depleted PBMCs, EBV-specific T cells were successfully generated and applied in clinical trials for lymphoma and viral infections.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Immunology
Wissam Charab, Matthew G. Rosenberger, Haridha Shivram, Justin M. Mirazee, Moses Donkor, Soumya R. Shekhar, Donjeta Gjuka, Kimberly H. Khoo, Jin Eyun Kim, Vishwanath R. Iyer, George Georgiou
Summary: Elevated levels of circulating immune complexes are associated with autoimmunity and worse prognoses in cancer. IgG-ICs inhibit the proliferation and differentiation of a subset of naive T cells while stimulating the division of another naive-like T cell subset. Phenotypic analysis revealed immature features in the inhibited T cell subset and transcriptional features indicative of a more differentiated phenotype in the stimulated T cell subset.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Hematology
Dalia E. Gaddis, Lindsey E. Padgett, Runpei Wu, Anh Nguyen, Chantel McSkimming, Huy Q. Dinh, Daniel J. Araujo, Angela M. Taylor, Coleen A. McNamara, Catherine C. Hedrick
Summary: The study found dysregulated expression of metabolism genes in CD4 T cells from atherosclerotic mice, and impaired glucose uptake, proliferation, and activation in these cells. Furthermore, a reduction in naive CD4 T cells and their proliferative capacity was observed in subjects with high cardiovascular disease, highlighting the dysfunction in CD4 T-cell metabolism and immune responses during atherosclerosis. Targeting metabolic pathways within naive CD4 T cells could offer novel therapeutic approaches for improving CD4 T-cell responses against atheroprogression.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Immunology
Monique M. Waldman, Jeremy T. Rahkola, Ashton L. Sigler, Jeffrey W. Chung, Benjamin A. S. Willett, Ross M. Kedl, Rachel S. Friedman, Jordan Jacobelli
Summary: Ena/VASP proteins play an important role in T cell-APC interactions, T cell activation, and T cell expansion.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Immunology
Rami Bechara, Alexia Feray, Marc Pallardy
Summary: Allergic reactions to drugs and chemicals are mediated by specific T cells and it is unclear whether there is a common occurrence of thymic selection of drug/chemical-specific T cells. Recent observations suggest that T-cell receptor recognition of hapten-modified peptides may play a crucial role in drug/chemical allergy. This understanding could lead to efficient strategies for allergy diagnosis and predicting the immunogenic potential of new chemicals.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Ying Liu, Yuying Ma, Jing Xu, Guangyue Zhang, Xiaocui Zhao, Zihao He, Lixia Wang, Na Yin, Min Peng
Summary: Liu et al. demonstrate the crucial role of VMP1 in the release of Ca2+ from the ER in resting cells. Deficiency of VMP1 in T cells results in ER Ca2+ overload and massive apoptosis. VMP1 is essential for maintaining ER Ca2+ homeostasis in naive T cells and its deficiency leads to ER stress, secondary Ca2+ overload in mitochondria, and defective T cell response.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Immunology
Fangfang Xiang, Xuesen Cao, Xiaohong Chen, Zhen Zhang, Xiaoqiang Ding, Jianzhou Zou, Bo Shen
Summary: Patients with end-stage renal disease are at high risk of cardiovascular and infectious diseases, with T-cell senescence playing a significant role. Systemic inflammation was found to be associated with T-cell senescence, and a reduction in naive T cells could predict cardiovascular events and infection episodes in hemodialysis patients.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Cell Biology
Jason L. Pugh, Sarah A. Foster, Alona S. Sukhina, Janka Petravic, Jennifer L. Uhrlaub, Jose Padilla-Torres, Tomonori Hayashi, Kei Nakachi, Megan J. Smithey, Janko Nikolich-Zugich
Article
Immunology
Kristin R. Renkema, June-Yong Lee, You Jeong Lee, Sara E. Hamilton, Kristin A. Hogquist, Stephen C. Jameson
JOURNAL OF EXPERIMENTAL MEDICINE
(2016)
Article
Immunology
Jennifer L. Uhrlaub, Megan J. Smithey, Janko Nikolich-Zugich
JOURNAL OF IMMUNOLOGY
(2017)
Article
Multidisciplinary Sciences
Megan J. Smithey, Vanessa Venturi, Miles P. Davenport, Adam S. Buntzman, Benjamin G. Vincent, Jeffrey A. Frelinger, Janko Nikolich-Zugich
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2018)
Article
Cell Biology
Emily L. Goldberg, Melissa J. Romero-Aleshire, Kristin R. Renkema, Melissa S. Ventevogel, Wade M. Chew, Jennifer L. Uhrlaub, Megan J. Smithey, Kirsten H. Limesand, Gregory D. Sempowski, Heddwen L. Brooks, Janko Nikolich-Zugich
Review
Geriatrics & Gerontology
Megan J. Smithey, Jennifer L. Uhrlaub, Gang Li, Milica Vukmanovic-Stejic, Arne N. Akbar, Janko Nikolich-Zugich
Article
Geriatrics & Gerontology
Paolo Sansoni, Rosanna Vescovini, Francesco F. Fagnoni, Arne Akbar, Ramon Arens, Yen-Ling Chiu, Luka Cicin-Sain, Julie Dechanet-Merville, Evelyna Derhovanessian, Sara Ferrando-Martinez, Claudio Franceschi, Daniela Frasca, Tamas Fuloep, David Furman, Effrossyni Gkrania-Klotsas, Felicia Goodrum, Beatrix Grubeck-Loebenstein, Mikko Hurme, Florian Kern, Daniele Lilleri, Miguel Lopez-Botet, Andrea B. Maier, Thomas Marandu, Arnaud Marchant, Catharina Mathei, Paul Moss, Aura Muntasell, Ester B. M. Remmerswaal, Natalie E. Riddell, Kathrin Rothe, Delphine Sauce, Eui-Cheol Shin, Amanda M. Simanek, Megan J. Smithey, Cecilia Soderberg-Naucler, Rafael Solana, Paul G. Thomas, Rene van Lier, Graham Pawelec, Janko Nikolich-Zugich
EXPERIMENTAL GERONTOLOGY
(2014)
Editorial Material
Immunology
Stephen C. Jameson, Kristin R. Renkema
Article
Immunology
Emily L. Goldberg, Megan J. Smithey, Lydia K. Lutes, Jennifer L. Uhrlaub, Janko Nikolich-Zugich
JOURNAL OF IMMUNOLOGY
(2014)
Article
Immunology
Jason L. Pugh, Alona S. Sukhina, Thomas M. Seed, Nancy R. Manley, Gregory D. Sempowski, Marcel R. M. van den Brink, Megan J. Smithey, Janko Nikolich- Zugich
JOURNAL OF IMMUNOLOGY
(2014)
Article
Immunology
Mladen Jergovic, Heather L. Thompson, Kristin R. Renkema, Megan J. Smithey, Janko Nikolich-Zugich
FRONTIERS IN IMMUNOLOGY
(2019)
Article
Immunology
Kristin R. Renkema, Matthew A. Huggins, Henrique Borges da Silva, Todd P. Knutson, Christy M. Henzler, Sara E. Hamilton
JOURNAL OF IMMUNOLOGY
(2020)
Article
Biology
Emily N. Truckenbrod, Kristina S. Burrack, Todd P. Knutson, Henrique Borges da Silva, Katharine E. Block, Stephen D. O'Flanagan, Katie R. Stagliano, Arthur A. Hurwitz, Ross B. Fulton, Kristin R. Renkema, Stephen C. Jameson
Summary: The study found that self-specific CD8(+) T cells in a physiological setting exhibit similar phenotypic and gene expression profiles, but show differences in function, such as enhanced self-tolerance in mice lacking Dct. This suggests that predicting CD8(+) T cell self-specificity is challenging based on precursor frequency, phenotype, or initial responsiveness, and that certain gene expression characteristics like reduced activation-induced CD25 expression may help identify functionally tolerant cells.