Article
Immunology
Lalit K. Beura, Milcah C. Scott, Mark J. Pierson, Vineet Joag, Sathi Wijeyesinghe, Matthew R. Semler, Clare F. Quarnstrom, Kathleen Busman-Sahay, Jacob D. Estes, Sara E. Hamilton, Vaiva Vezys, David H. O'Connor, David Masopust
Summary: Lymphocytic choriomeningitis virus (LCMV) is a natural mouse pathogen that can cause chronic infection. In this study, a new strain called LCMV-Minnesota (LCMV-MN) was isolated and characterized. Infection with LCMV-MN in laboratory mice resulted in viral persistence, with CD8(+) T cells showing characteristics of exhausted cells. This study provides insights into the immune response to chronic infections and the regulation of response to PD-1 blockade.
JOURNAL OF IMMUNOLOGY
(2022)
Review
Immunology
B. Rhodes Ford, Amanda C. Poholek
Summary: Exhaustion is a state of CD8 T cell differentiation that occurs in chronic environments, such as tumors, chronic viral infections, and autoimmunity. The epigenetic changes associated with exhaustion are distinct from effector and memory cell differentiation, indicating that early signals modify the epigenome to promote a trajectory toward dysfunction. Understanding the relationship between exhaustion-promoting signals and epigenetic changes is important for future therapeutic opportunities.
JOURNAL OF IMMUNOLOGY
(2023)
Article
Immunology
Sacha Horn, Dennis Borrero-Wolff, Manuel Ritter, Kathrin Arndts, Anna Wiszniewsky, Linda Batsa Debrah, Alexander Y. Debrah, Jubin Osei-Mensah, Mkunde Chachage, Achim Hoerauf, Inge Kroidl, Laura E. Layland
Summary: CD8(+) T cells play a crucial role in clearing viral infections and recent research points to their significance in parasitic diseases too. This study highlights distinct exhausted CD8(+) T-cell subsets in individuals suffering from filarial lymphedema, suggesting that enhanced inflammation and constant immune activation may drive exhaustion of these cells.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Immunology
Andrea C. Pichler, Nadege Carrie, Marine Cuisinier, Samira Ghazali, Allison Voisin, Pierre-Paul Axisa, Marie Tosolini, Celine Mazzotti, Dominic P. Golec, Sabrina Maheo, Laura do Souto, Ruchan Ekren, Eve Blanquart, Lea Lemaitre, Virginie Feliu, Marie-Veronique Joubert, Jennifer L. Cannons, Camille Guillerey, Herve Avet-Loiseau, Tania H. Watts, Benoit L. Salomon, Olivier Joffre, Yenkel Grinberg-Bleyer, Pamela L. Schwartzberg, Liliana E. Lucca, Ludovic Martinet
Summary: CD137 (4-1BB) is a promising target for cancer immunotherapy. It modulates the infiltration of CD8+ exhausted T cells expressing inhibitory receptors into tumors. CD137 signaling stimulates the proliferation and differentiation of Tex precursor cells through NF-KB subunits RelA and cRel and Tox-dependent chromatin remodeling. Understanding T cell exhaustion is crucial for cancer and infectious disease treatment. CD137 is identified as a critical regulator of Tex cell expansion and differentiation with broad therapeutic potential.
Article
Multidisciplinary Sciences
Mayura Wagle, Stephin J. Vervoort, Madison J. Kelly, Willem Van der Byl, Timothy J. Peters, Ben P. Martin, Luciano G. Martelotto, Simone Nuessing, Kelly M. Ramsbottom, James R. Torpy, Deborah Knight, Sinead Reading, Kevin Thia, Lisa A. Miosge, Debbie R. Howard, Renee Gloury, Sarah S. Gabriel, Daniel T. Utzschneider, Jane Oliaro, Jonathan D. Powell, Fabio Luciani, Joseph A. Trapani, Ricky W. Johnstone, Axel Kallies, Christopher C. Goodnow, Ian A. Parish
Summary: Chronic antigenic stimulation induces the expression of EGR2, which in turn affects the epigenetic and transcriptional identity of exhausted T cells.
NATURE COMMUNICATIONS
(2021)
Article
Virology
Amanda L. Gill, William H. Hudson, Rajesh M. Valanparambil, Eunseon Ahn, Donald J. McGuire, Andreas Wieland, Daniel T. McManus, Haydn T. Kissick, Rama S. Akondy, Rafi Ahmed
Summary: A better understanding of long-lived memory CD8 T cell differentiation is necessary due to increased demand for novel vaccination strategies. Using a mouse model of acute LCMV infection, we conducted an in-depth, longitudinal analysis of memory CD8 T cell subsets, examining their phenotype, transcriptional programming, and anatomical location in the spleen. We characterized a comprehensive memory phenotype associated with higher CD28 expression and found distinct localization programs within the spleen for memory subsets. These findings suggest that memory formation and survival may be influenced by location, emphasizing the importance of considering memory phenotypes and their trafficking for robust memory responses following vaccination.
JOURNAL OF VIROLOGY
(2023)
Article
Immunology
Junghwa Lee, Kyungmin Lee, Hyeonjin Bae, Kunhee Lee, Solhwi Lee, Junhui Ma, Kyungjo Jo, Ijun Kim, ByulA Jee, Minyong Kang, Se Jin Im
Summary: In chronic infections and cancer, exhausted CD8 T cells display heterogeneous subpopulations. TCF1+PD-1+ progenitor exhausted CD8 T cells (Tpex) have the ability to self-renew and differentiate into Tim-3+PD-1+ terminally differentiated CD8 T cells. Tpex cells are crucial for maintaining a pool of antigen-specific CD8 T cells during persistent antigenic stimulation and are responsive to PD-1-targeted therapy.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Ryan Zander, Weiguo Cui
Summary: Reinvigorating exhausted CD8+ T cells is a major goal in immunotherapy for chronic viral infection and cancer. Recent advances have shown that exhausted CD8+ T cells exhibit heterogeneity and can differentiate into either terminally differentiated effector cells or remain exhausted. The potential therapeutic implications of redirecting progenitor CD8+ T cell differentiation towards effector cells are also discussed.
TRENDS IN IMMUNOLOGY
(2023)
Review
Oncology
Thomas Gebhardt, Simone L. Park, Ian A. Parish
Summary: This article discusses the similarities and differences in the regulation and function of stem-like exhausted T cells and memory T cells, and explores their importance in cancer immunity.
NATURE REVIEWS CANCER
(2023)
Article
Immunology
Nadia Bannoud, Tomas Dalotto-Moreno, Lucia Kindgard, Pablo A. Garcia, Ada G. Blidner, Karina V. Marino, Gabriel A. Rabinovich, Diego O. Croci
Summary: This study highlights the reciprocal regulation between hypoxia, angiogenesis, and immunosuppression in tumor progression and anti-tumor therapies. The findings suggest a rational basis for optimizing synergistic combinations of antiangiogenic and immunotherapeutic strategies to enhance treatment efficacy.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Huarong Zhou, Bei Jia, Charyguly Annageldiyev, Kentaro Minagawa, Chenchen Zhao, Shin Mineishi, W. Christopher Ehmann, Seema G. Naik, Joseph Cioccio, Baldeep Wirk, Natthapol Songdej, Kevin L. Rakszawski, Myles S. Nickolich, Jianzhen Shen, Hong Zheng
Summary: Acute myeloid leukemia (AML) is a devastating blood cancer with a need for new effective treatments. Immunotherapy targeting T cell exhaustion by blocking inhibitory pathways, such as PD-1, is promising but has been disappointing in clinical studies with AML patients. CD26(low)PD-1(+) CD8 T cells have been found to be associated with AML progression and exhaustion, suggesting a prognostic and predictive value of CD26 in AML.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Gaayathri Ariyakumar, Sarah Gee, Abhishek Das, Shraddha Kamdar, Rachel M. Tribe, Deena L. Gibbons
Summary: This study reveals rapid changes in immune cell populations within hours of birth, indicating immediate mobilization of the immune system post birth. Therefore, blood sampling should begin as soon after birth as possible to study the trajectory of immune development.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Laura Campisi, Shahab Chizari, Jessica S. Y. Ho, Anastasia Gromova, Frederick J. Arnold, Lorena Mosca, Xueyan Mei, Yesai Fstkchyan, Denis Torre, Cindy Beharry, Marta Garcia-Forn, Miguel Jimenez-Alcazar, Vladislav A. Korobeynikov, Jack Prazich, Zahi A. Fayad, Marcus M. Seldin, Silvia De Rubeis, Craig L. Bennett, Lyle W. Ostrow, Christian Lunetta, Massimo Squatrito, Minji Byun, Neil A. Shneider, Ning Jiang, Albert R. La Spada, Ivan Marazzi
Summary: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that affects motor neurons and muscle control, with different gene mutations defining subtypes. A specific immune signature has been identified in ALS4 patients, potentially serving as a biomarker for disease progression.
Article
Multidisciplinary Sciences
Laura Campisi, Shahab Chizari, Jessica S. Y. Ho, Anastasia Gromova, Frederic Arnold, Lorena Mosca, Xueyan Mei, Yesai Fstkchyan, Denis Torre, Cindy Beharry, Marta Garcia-Forn, Miguel Jimenez-Alcazar, Vladislav A. Korobeynikov, Jack Prazich, Zahi A. Fayad, Marcus M. Seldin, Silvia De Rubeis, Craig L. Bennett, Lyle W. Ostrow, Christian Lunetta, Massimo Squatrito, Minji Byun, Neil A. Shneider, Ning Jiang, Albert R. La Spada, Ivan Marazzi
Summary: This study describes the presence of clonally expanded T-EMRA CD8 T cells in ALS4 knock-in mice and ALS4 patients, which may be related to disease progression and anti-glioma immunity. The results provide evidence for unraveling the disease mechanisms and serve as a potential biomarker of ALS4.
Article
Cell Biology
Domenico Lo Tartaro, Antonio Camiro-Zuniga, Milena Nasi, Sara De Biasi, Marco A. Najera-Avila, Maria Del Rocio Jaramillo-Jante, Lara Gibellini, Marcello Pinti, Anita Neroni, Cristina Mussini, Luis E. Soto-Ramirez, Juan J. Calva, Francisco Belaunzaran-Zamudio, Brenda Crabtree-Ramirez, Christian Hernandez-Leon, Juan L. Mosqueda-Gomez, Samuel Navarro-Alvarez, Santiago Perez-Patrigeon, Andrea Cossarizza
Summary: This study focused on the impact of HIV infection on T- and B-cell subsets during the early phase of infection, showing that ART treatment can reduce HIV DNA content in memory T cells and lead to significant changes in CD4+ and CD8+ T memory stem cells.