Article
Immunology
Bernhard Reus, Stefano Caserta, Martin Larsen, George Morrow, Aalia Bano, Michael Hallensleben, Chakravarthi Rajkumar, Alejandra Pera, Florian Kern
Summary: The study provides a detailed analysis of CMV-specific T-cell responses in elderly individuals, showing that men have larger and more pro-inflammatory T-cell responses with a more prominent accumulation of CMV-specific memory T-cells. There were similar levels of T-cell polyfunctionality and differentiation between sexes.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Geriatrics & Gerontology
David Goldeck, Wim Adriaensen, Lilly Oettinger, Bert Vaes, Gijs van Pottelbergh, Jean-Marie Degryse, Klaus Hamprecht, Catharina Mathei, Graham Pawelec
Summary: In this study, the authors examined the association between immune cell phenotypes and changes in ADL, geriatric depression score, Mini-Mental State Examination, and Short Physical Performance Battery over an 18-month follow-up period in the very old population. They found that higher frequencies of B cells and late-differentiated CD8(+) T cells were associated with worsened ADL over the preceding 18 months, but did not find significant associations with other immune cell types or other geriatric assessment parameters. These results suggest that certain adaptive immune parameters may be linked to declines in functional abilities in the elderly.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2021)
Article
Chemistry, Multidisciplinary
Songbo Zhao, Jiazhi Duan, Yalin Lou, Ruyun Gao, Shanshan Yang, Piming Wang, Chunhua Wang, Lin Han, Minghuan Li, Chunhong Ma, Xiaohong Liang, Hong Liu, Yuanhua Sang, Lifen Gao
Summary: A novel immunotherapy approach utilizing NK cells conjugated with magnetic nanoparticles has been developed for treating solid tumors, demonstrating improved tumor targeting and inhibition capabilities through magnetic field guidance.
Article
Medicine, Research & Experimental
Yan Zhang, Ada W. C. Yan, Lies Boelen, Linda Hadcocks, Arafa Salam, Daniel Padrosa Gispert, Loiza Spanos, Laura Mora Bitria, Neda Nemat-Gorgani, James A. Traherne, Chrissy Roberts, Danai Koftori, Graham P. Taylor, Daniel Forton, Paul J. Norman, Steven G. E. Marsh, Robert Busch, Derek C. Macallan, Becca Asquith
Summary: Inhibitory killer cell immunoglobulin-like receptors (iKIRs) can modulate T cell responses and affect T cell lifespan. The iKIR-ligand genotype is significantly associated with CD8+ T cell lifespan, with individuals having 4 iKIR-ligand gene pairs having double the lifespan compared to individuals with 2 gene pairs. The iKIR-ligand genotype also alters the immune aging phenotype of CD8+ and CD4+ T cells.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Immunology
Daan K. J. Pieren, Noortje A. M. Smits, Rimke J. Postel, Vinitha Kandiah, Jelle de Wit, Josine van Beek, Debbie van Baarle, Teun Guichelaar
Summary: Aging leads to decreased immune responsiveness, known as immunosenescence. This study identifies novel markers associated with immunosenescence in CD8(+) T cells and shows that these features become prominent even in the earlier differentiation states of these cells.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Ahto Salumets, Liina Tserel, Anna P. Rumm, Lehte Turk, Kulli Kingo, Kai Saks, Astrid Oras, Raivo Uibo, Riin Tamm, Hedi Peterson, Kai Kisand, Part Peterson
Summary: Age-related changes in T-cell populations play an important role in immunosenescence. CD8(+) TEMRA cells and their subsets have characteristics of cellular senescence and increase in older individuals and age-related chronic inflammatory diseases. CD8(+) TEMRA proportions correlate with cytomegalovirus (CMV) antibody levels but not with chronological age. TRANCE/RANKL levels are associated with differentiated T-cell populations, including CD8(+) TEMRA and its CD28(-) subsets. Deep-amplicon bisulfite sequencing can be used to predict CD8(+) TEMRA cell proportions as a biomarker of immunosenescence.
Review
Biochemistry & Molecular Biology
Takahiro Uchida, Shuhji Seki, Takashi Oda
Summary: Natural killer T (NKT) cells and NK cells have important roles in antitumor and antimicrobial functions. They are involved in various renal diseases, including acute kidney injury (AKI). NKT cells in mice are activated by specific ligands, cytokines, and bacterial components, leading to AKI. Both renal vascular endothelial cell injury (via perforin-mediated pathway) and tubular epithelial cell injury (via tumor necrosis factor-alpha/Fas ligand pathway) are independently involved in the pathogenesis of AKI. NK cells complement the functions of NKT cells in the development of infection-associated AKI. Human CD56(+) T cells, which are functional counterparts of murine NKT cells, and a subpopulation of CD56(+) NK cells damage intrinsic renal cells in vitro upon activation, possibly through mechanisms similar to those in mice. These cells are also thought to be involved in the acute exacerbation of pre-existing glomerulonephritis triggered by infection in humans, and their roles in sepsis-associated AKI are currently under investigation. In this review, we provide an overview of recent advances in the understanding of the association among infections, NKT and NK cells, and kidney injury, which is much more profound than previously considered. The important role of liver macrophages in the activation of NKT cells is also introduced.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Immunology
Lore Billiet, Laurenz De Cock, Guillem Sanchez Sanchez, Rupert L. Mayer, Glenn Goetgeluk, Stijn De Munter, Melissa Pille, Joline Ingels, Hanne Jansen, Karin Weening, Eva Pascal, Killian Raes, Sarah Bonte, Tessa Kerre, Niels Vandamme, Ruth Seurinck, Jana Roels, Marieke Lavaert, Filip Van Nieuwerburgh, Georges Leclercq, Tom Taghon, Francis Impens, Bjorn Menten, David Vermijlen, Bart Vandekerckhove
Summary: Billiet et al. identify a well-defined but heterogeneous unconventional TCR alpha beta(+) lineage mainly confined to CD8(+) Helios(+) T cells, which represents the post-thymic progeny of CD10(+) PD-1(+) precursors in humans. These unconventional T cells (UTCs) in thymus and blood share a common developmental trajectory, characterized by hallmark transcription factors (ZNF683 and IKZF2) and a polycolonal TCR repertoire with autoreactive features. The UTC lineage can be identified in adult blood and intestinal tissues.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Cell Biology
Kyeong Jin Yoon, Aram Ahn, Soo Hong Park, Seung Hee Kwak, Seong Eun Kwak, Wonsang Lee, Yong Ryoul Yang, Minji Kim, Hyun Mu Shin, Hang-Rae Kim, Hyo Youl Moon
Summary: This study confirmed that 4 weeks of treadmill exercise can significantly improve metabolic function in aged mice, including increased lean mass and decreased fat mass, while decreasing the expression level of the senescence marker p16 in white adipose tissue. Exercise also induced changes in immune-cell subsets in the stromal vascular fraction of WAT, as well as activating pathways involved in the interaction between WAT and immune cells, particularly NK cells, in aged mice. These results suggest that exercise has a profound effect on immune-cell distribution and senescent-cell scavenging in WAT of aged mice, ultimately affecting overall energy metabolism towards a more youthful state.
Article
Cell Biology
Dorina Zoephel, Adrian Angenendt, Lea Kaschek, Keerthana Ravichandran, Chantal Hof, Sandra Janku, Markus Hoth, Annette Lis
Summary: A variety of intrinsic and extrinsic factors contribute to the altered efficiency of CTLs in elderly organisms. In this study, the cytotoxic ability of CD8(+) T cells in aging was investigated, and it was found that CD8(+) T cells from elderly mice exhibited faster killing kinetics compared to those from adult mice. Further analysis revealed that CD8(+) T cells from elderly mice had increased numbers of cells with granule fusion and higher levels of perforin and granzyme, making them very efficient killers.
Article
Immunology
Stephan Fuhrmann, Bernhard Reus, Oliver Frey, Alejandra Pera, Louis J. Picker, Florian Kern
Summary: The effect of CMV infection on non-CMV-specific T-cells is limited to a minority of individuals and is not closely related to the degree of memory subset differentiation of CMV-specific T-cells. Unknown predisposing factors might determine to what extent CMV infection affects non-CMV-specific T-cell differentiation.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Dmytro Shytikov, Deepak Rohila, Dan Li, Pengfei Wang, Mei Jiang, Mingxu Zhang, Qin Xu, Linrong Lu
Summary: The role of Ly49(+)CD8 T-cells in the immune system and the mechanism of Ly49 expression on CD8 T-cells are still unclear. Studies have shown that Ly49(+)CD8 T-cells express different receptors compared to NK cells and play important roles in immune response and viral infection.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Cell Biology
Ashley Brauning, Michael Rae, Gina Zhu, Elena Fulton, Tesfahun Dessale Admasu, Alexandra Stolzing, Amit Sharma
Summary: Aging is a major risk factor for chronic diseases, and immunosenescence, including age-related natural killer (NK) cell dysfunction, plays a significant role in age-related morbidity and mortality. NK cell dysfunction is implicated in the increasing burden of infection, malignancy, inflammatory disorders, and senescent cells with age. Understanding the interplay between systemic inflammation, senescence burden, and NK cell dysfunction can potentially lead to therapies countering age-related diseases and underlying biological aging processes.
Article
Medicine, General & Internal
Leah Zuroff, Ayman Rezk, Koji Shinoda, Diego A. Espinoza, Yehezqel Elyahu, Bo Zhang, Andrew A. Chen, Russell T. Shinohara, Dina Jacobs, Roy N. Alcalay, Thomas F. Tropea, Alice Chen-Plotkin, Alon Monsonego, Rui Li, Amit Bar-Or
Summary: In the study comparing untreated MS patients with normal controls, it was found that MS patients exhibited early and persistent redistribution of naive and memory CD4 T-cell compartments. While most CD4 and CD8 T-cell aging trajectories were similar between groups, MS patients demonstrated abnormal age-associated increases, particularly in patients over 60.
Article
Immunology
Alejandra Garcia-Torre, Eva Bueno-Garcia, Rocio Lopez-Martinez, Beatriz Rioseras, Beatriz Diaz-Molina, Jose Luis Lambert, Covadonga Quiros, Sara Alonso-Alvarez, Rebeca Alonso-Arias, Marco A. Moro-Garcia
Summary: The study revealed that patients with CHF have elevated levels of pro-inflammatory cytokines, especially in CMV-positive patients, which are associated with functional status. Additionally, there is a positive correlation between anti-CMV antibody levels and cytokine levels in these patients.
FRONTIERS IN IMMUNOLOGY
(2021)
Editorial Material
Immunology
Stefano Caserta, Alejandra Pera
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Geriatrics & Gerontology
Martina Formentini, Ana Navas, Fakhri Hassouneh, Nelson Lopez-Sejas, Corona Alonso, Raquel Tarazona, Rafael Solana, Alejandra Pera
Summary: Immunosenescence affects innate and adaptive immunity, with chronic CMV infection contributing to early immunosenescence. The markers CD57, CD300a, and CD161 define distinct T-cell subsets, showing varied functionality and molecular signatures. Different T-cell populations based on these markers have implications for disease risk in older adults.
JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
(2021)
Review
Immunology
Alexander Batista-Duharte, Alejandra Pera, Salvador F. Alino, Rafael Solana
Summary: Regulatory T cells play a crucial role in maintaining immune tolerance, but their excessive activity may reduce the effectiveness of vaccines. Increased activity of regulatory T cells in older adults may contribute to the observed lower vaccine effectiveness in this age group.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Fakhri Hassouneh, David Goldeck, Alejandra Pera, Diana van Heemst, P. Eline Slagboom, Graham Pawelec, Rafael Solana
Summary: The study revealed that CMV infection and aging impact the function and phenotype of T-cells, with CD57+ T-cells being more polyfunctional than CD57- T-cells. The expansion of cytotoxic T-cells is mainly associated with CMV infection, highlighting the significant role of CMV in driving the expansion of highly polyfunctional CD57+ T-cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Immunology
Bernhard Reus, Stefano Caserta, Martin Larsen, George Morrow, Aalia Bano, Michael Hallensleben, Chakravarthi Rajkumar, Alejandra Pera, Florian Kern
Summary: The study provides a detailed analysis of CMV-specific T-cell responses in elderly individuals, showing that men have larger and more pro-inflammatory T-cell responses with a more prominent accumulation of CMV-specific memory T-cells. There were similar levels of T-cell polyfunctionality and differentiation between sexes.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Pharmacology & Pharmacy
Alexander Batista-Duharte, Fakhri Hassouneh, Pablo Alvarez-Heredia, Alejandra Pera, Rafael Solana
Summary: The combination of immune checkpoint inhibitors (ICIs) with vaccines has shown promise in improving vaccine immunogenicity and efficacy. Most studies have focused on anti-tumor vaccines combined with monoclonal antibodies targeting specific checkpoints. However, new strategies using ICIs as molecular adjuvants hold great potential for future advances in vaccine research.
Article
Biochemistry & Molecular Biology
Pablo Alvarez-Heredia, Jose Joaquin Dominguez-del-Castillo, Irene Reina-Alfonso, Carmen Gutierrez-Gonzalez, Fakhri Hassouneh, Alexander Batista-Duharte, Antonio Trujillo-Aguilera, Rosalia Lopez-Romero, Ignacio Munoz, Rafael Solana, Alejandra Pera
Summary: Aortic stenosis is a common cardiac disease characterized by valvular calcification, fibrosis, and inflammation. Recent studies suggest that it is an active inflammatory atherosclerotic-like process involving immune cells and persistent antigens. However, the study of calcified aortic valves has been limited by histological and immunohistochemical methods. This study presents a cytometry-based protocol that allows for the identification and quantification of inflammatory leukocytes in aortic valve explants, providing a more in-depth analysis of cell markers. This protocol can be applied to other cardiac diseases with an inflammatory component.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Pablo Alvarez-Heredia, Irene Reina-Alfonso, Jose Joaquin Dominguez-del-Castillo, Carmen Gutierrez-Gonzalez, Fakhri Hassouneh, Alexander Batista-Duharte, Ana-Belen Perez, Raquel Tarazona, Rafael Solana, Alejandra Pera
Summary: Coinfection with SARS-CoV-2 and CMV leads to accelerated T cell senescence and increased risk of cardiovascular disease. SARS-CoV-2 vaccination appears to provide some protection against this phenomenon.
JOURNAL OF INFECTIOUS DISEASES
(2023)
Article
Immunology
Sofia Carreira-Santos, Nelson Lopez-Sejas, Marina Gonzalez-Sanchez, Eva Sanchez-Hernandez, Alejandra Pera, Fakhri Hassouneh, Esther Duran, Rafael Solana, Javier G. Casado, Raquel Tarazona
Summary: This study provides a deep phenotypic characterization of in vitro-expanded CIML NK cells. Moreover, the correlations found between NK cell receptors and degranulation capacity of CIML NK cells allowed the identification of several biomarkers that could be useful in clinical settings.
FRONTIERS IN IMMUNOLOGY
(2023)
Meeting Abstract
Immunology
Alejandra Pera, Frances Kirkham, Amanda M. Simanek, Aalia Bano, George Morrow, Bernhard Reus, Stefano Caserta, Helen E. Smith, Kevin A. Davies, Chakravarthi Rajkumar, Florian Kern
EUROPEAN JOURNAL OF IMMUNOLOGY
(2021)
Article
Medicine, Research & Experimental
Frances Kirkham, Alejandra Pera, Amanda M. Simanek, Aalia Bano, George Morrow, Bernhard Reus, Stefano Caserta, Helen E. Smith, Kevin A. Davies, Chakravarthi Rajkumar, Florian Kern
Summary: The study found that CMV infection increases cardiovascular disease risk in older men, potentially mediated by the increased proportion of CD4 memory T-cells, especially among CMV-positive individuals. Given the high prevalence of CMV globally, novel strategies may be needed to mitigate the increased CVD risk associated with CMV.