bims-imseme Biomed News
on Immunosenescence and T cell metabolism
Issue of 2025–08–03
seventeen papers selected by
Pierpaolo Ginefra, Ludwig Institute for Cancer Research
  1. NAD + metabolism and function in innate and adaptive immune cells.
  2. Aberrant protein translation promotes T cell exhaustion.
  3. Metabolic and Epigenetic Control of CD8+ T Cell Exhaustion: The Acetate-to-Citrate Switch.
  4. UPF1 attenuates CD8+ T cell exhaustion in glioma by destabilizing CD52 mRNA.
  5. Early-life human CD8+ T cells exhibit rapid, short-lived effector responses and a unique transcription factor landscape.
  6. Epigenetic priming as a driver of memory recall and dysfunction in T cells.
  7. Exercise induces metabolic changes in the gut microbiota that enhance anti-tumour T cell responses.
  8. Sucralose consumption ablates cancer immunotherapy response through microbiome disruption.
  9. Lymph-node-derived stem-like but not tumor-tissue-resident CD8+ T cells fuel anticancer immunity.
  10. Manufacturing of CRISPR-edited primary mouse CAR T cells for cancer immunotherapy.
  11. Berberine alleviates T cell-driven lung inflammation by inhibiting cytokine secretion and regulating pulmonary microbiota.
  12. Host-microbe interactions in NAD+ metabolism.
  13. Innate-like memory T cells rapidly emerge in humans after gene therapy for SCID-X1 test.
  14. CARMIL2 deficiency disrupts activation-induced metabolic reprogramming in T cells, and is partially rescued by glutamine supplementation.
  15. CD4 T cell therapy counteracts inflammaging and senescence by preserving gut barrier integrity.
  16. Spatial Organisation of Tumour cDC1 States Correlates with Effector and Stem-Like CD8+ T Cells Location.
  17. CD8+ T Cells You Should Know about in Autoimmunity: Current Paradigms of T Cell Pathogenesis in Autoimmune Disease.
  1. J Inflamm (Lond). 2025 Aug 01. 22(1): 30
    NAD + metabolism and function in innate and adaptive immune cells.
    Rebecca Mann, Victoria Stavrou, Sarah Dimeloe.
      Nicotinamide adenine dinucleotide (NAD+) plays a central role in cellular metabolism and energy production, supporting many biological processes. Recent studies highlight the significance of NAD + in regulation of immune cell function, with implications for our understanding of immune homeostasis, inflammation, and disease. This review reports our current understanding on the role of NAD + in the immune system, specifically in macrophages and T cells, facilitating their metabolic reprogramming during differentiation and activation. It offers an overview of NAD + biosynthesis within these immune cells, describes its role in the modulation of immune cell metabolism and effector function, and highlights potential therapeutic applications of NAD + modulation in immunological disorders including autoimmune diseases and cancer.
    DOI:  https://doi.org/10.1186/s12950-025-00457-7
  2. Nat Immunol. 2025 Jul 25.
    Aberrant protein translation promotes T cell exhaustion.
      
    DOI:  https://doi.org/10.1038/s41590-025-02244-1
  3. MedComm (2020). 2025 Aug;6(8): e70307
    Metabolic and Epigenetic Control of CD8+ T Cell Exhaustion: The Acetate-to-Citrate Switch.
    Xiaoyi Lei, Wei Zhang, Dunfang Zhang.
      
    DOI:  https://doi.org/10.1002/mco2.70307
  4. Tissue Cell. 2025 Jul 29. pii: S0040-8166(25)00338-6. [Epub ahead of print]97 103058
    UPF1 attenuates CD8+ T cell exhaustion in glioma by destabilizing CD52 mRNA.
    Junwei Duan, Long Zhao, Jie Duan, Hua Peng, Chao Hu, Binbin Yang, Jingtian Huyang.
      CD8+ T cell exhaustion has emerged as a challenge for progression and immunotherapy in nearly all of tumors including glioma. Recent studies revealed that UPF1 might play a suppressive role in glioma progression, however the underlying mechanism is unclear. Here, exhausted CD8+ T cells (CD8+ Tex) and total CD8+ T cells were isolated from PBMCs of glioma patients and healthy volunteers. We found that UPF1 was downregulated in CD8+ Tex compared to total CD8+ T cells. Glioma patients with elevated UPF1 expression in CD8+ T cells showed significantly prolonged overall survival. CD8+ T cells, or those with UPF1 overexpression/silencing, were co-cultured with U251 glioma cells to evaluate their impact on U251 cell malignant progression. UPF1 overexpression enhanced CD8+ T cell anti-tumor activity by promoting anti-tumor cytokine secretion and suppressing immune checkpoint factor expression. Mechanistically, UPF1 bound to CD52 mRNA, reducing its stability and protein levels, thereby alleviating CD52-mediated CD8+ T cell exhaustion. CD52 overexpression reversed the anti-tumor effects of UPF1 on CD8+ T cells. An in situ glioma mouse model was established by injecting GL261 cells into the ventricles of wild-type (WT) and T cell-specific UPF1 conditional knockout (UPF1 cKO) mice. UPF1 cKO mice showed increased tumor burden compared to WT mice, which was rescued by UPF1 restoration. In conclusion, UPF1 attenuates CD8+ T cell exhaustion and suppresses glioma progression by destabilizing CD52 mRNA.
    Keywords:  CD52 mRNA stability; CD8(+) T cell exhaustion; Glioma; Immune checkpoint; UPF1
    DOI:  https://doi.org/10.1016/j.tice.2025.103058
  5. Proc Natl Acad Sci U S A. 2025 Aug 05. 122(31): e2421106122
    Early-life human CD8+ T cells exhibit rapid, short-lived effector responses and a unique transcription factor landscape.
    Nina N Brodsky, Monisha Chakder, Dinesh Babu Uthaya Kumar, Anis Barmada, Julia Wang, Weihong Gu, Oluwabunmi Olaloye, Anjali Ramaswamy, Aanchal Wats, Liza Konnikova, Carrie L Lucas.
      Neonates and infants are distinct in their clinical and cellular responses to viral infections, with neonatal CD8+ T cells displaying innate-like characteristics and a low threshold for T cell receptor activation. However, specific molecular programs that drive these unique responses are incompletely understood, particularly in humans, and targetable pathways to modulate viral illness in this vulnerable population remain to be elucidated. Early-life immune responses may be developmentally programmed to prioritize avoidance of tissue immunopathology, especially while maternal immunoglobulin provides passive immunity. We set out to define the unique response characteristics and transcription factor landscape of neonatal human CD8+ T cells. Here, we report evidence that naïve neonatal human CD8+ T cells are poised for an accelerated effector switch, with elevations of killer cell lectin-like receptor G1 (KLRG1), killer cell lectin-like receptor B1 (KLRB1/CD161), Fc epsilon receptor I-gamma (FCER1G), DNAX accessory molecule-1 (DNAM1/CD226), granzymes, tumor necrosis factor alpha (TNFα), interleukin 2 (IL-2), and glycolysis compared to naïve adult CD8+ T cells. Further, rapid proliferation and cell death occur upon activation of neonatal CD8+ T cells, with cell viability largely rescued by IL-2 or IL-7. These features are coupled with a unique transcription factor landscape, including high expression of thymocyte selection associated high mobility group box (TOX) and HELIOS (IKZF2), and these signatures continue in postnatal life until at least 2 mo of age. We conclude that early-life human CD8+ T cells maintain a unique transcriptional state associated with an accelerated effector switch and short-lived effector program, revealing key nodes of regulation relevant for the unique immunobiology of neonatal humans.
    Keywords:  CD8+ T cell; differentiation; effector; neonate; transcription factor
    DOI:  https://doi.org/10.1073/pnas.2421106122
  6. J Exp Med. 2025 Sep 01. pii: e20241433. [Epub ahead of print]222(9):
    Epigenetic priming as a driver of memory recall and dysfunction in T cells.
    Mieke Metzemaekers, Niels J Rinzema, Ralph Stadhouders.
      T cells are essential for protective immunity against pathogens and malignancies. While the initial activation of a naive T cell is slow, antigen-experienced or memory T cells mount near-immediate protective responses through their remarkable capacity to instantaneously reactivate inflammatory gene programs upon antigen rechallenge. Evidence is emerging that this immunological memory is underpinned by dynamic changes at the chromatin level or epigenome of T cells. Here, we review recent findings on how epigenetic mechanisms are a driving force guiding initial T cell activation and differentiation, and durably endow memory T cells with the ability to remember gene regulatory processes essential for high-magnitude protective immune responses. We discuss the molecular programs that may be involved in the establishment and maintenance of chromatin-based information in memory T cells during homeostasis, and how undesired epigenetic priming may program T cells for dysfunction in patients with chronic immune-related disease and cancer.
    DOI:  https://doi.org/10.1084/jem.20241433
  7. Nat Rev Immunol. 2025 Jul 28.
    Exercise induces metabolic changes in the gut microbiota that enhance anti-tumour T cell responses.
    Yvonne Bordon.
      
    DOI:  https://doi.org/10.1038/s41577-025-01217-7
  8. Cancer Discov. 2025 Jul 30.
    Sucralose consumption ablates cancer immunotherapy response through microbiome disruption.
    Kristin M Morder, Madison Nguyen, Drew N Wilfahrt, Zakaria Larbi Dahmani, Ansen Bp Burr, Bingxian Xie, Michael Morikone, Hector Nieves-Rosado, William G Gunn, Drew E Hurd, Hong Wang, Steven J Mullett, Kaitlin Bossong, Stacy L Gelhaus, Dhivyaa Rajasundaram, Lawrence P Kane, Greg M Delgoffe, Jishnu Das, Diwakar Davar, Abigail E Overacre-Delgoffe.
      Gut microbiota composition is directly associated with response to immunotherapies in cancer. How the diet impacts the gut microbiota and downstream immune responses to cancer remains unclear. Here, we show that consumption of a common non-nutritive sweetener, sucralose, modifies microbiome composition, restricts T cell metabolism and function, and limits immunotherapy response in preclinical models of cancer and advanced cancer patients treated with anti-PD-1 based immune checkpoint inhibitors (ICIs). Sucralose consumption is associated with a reduction in microbiota-accessible arginine, and amino acid supplementation or fecal microbiome transfer (FMT) from anti-PD-1 responder mice completely restores T cell function and immunotherapy response. Overall, sucralose consumption destabilizes the gut microbiota, resulting in compromised T cell function and ablated ICI response in cancer.
    DOI:  https://doi.org/10.1158/2159-8290.CD-25-0247
  9. Nat Immunol. 2025 Aug;26(8): 1367-1383
    Lymph-node-derived stem-like but not tumor-tissue-resident CD8+ T cells fuel anticancer immunity.
    Sharanya K M Wijesinghe, Lisa Rausch, Sarah S Gabriel, Giovanni Galletti, Marco De Luca, Lei Qin, Lifen Wen, Carlson Tsui, Kevin Man, Leonie Heyden, Teisha Mason, Lewis D Newland, Andrew Kueh, Yang Liao, David Chisanga, Julian Swatler, Emanuele Voulaz, Giuseppe Marulli, Valentina Errico, Agnese Losurdo, Gustavo R Rossi, Fernando Souza-Fonseca-Guimaraes, Nicholas D Huntington, Thomas Gebhardt, Daniel T Utzschneider, Marco J Herold, Wei Shi, Jan Schroeder, Enrico Lugli, Axel Kallies.
      CD8+ T cell-mediated tumor control and efficacy of immune checkpoint blockade (ICB) are associated with both precursors of exhausted T (TPEX) cells and tissue-resident memory T cells. Their relationships and relative contribution to tumor control, however, are insufficiently understood. Using single-cell RNA sequencing and genetic mouse models, we systematically dissected the heterogeneity and function of cytotoxic T cells in tumors and tumor-draining lymph nodes (tdLNs). We found that intratumoral TCF1+ TPEX cells and their progeny acquired a tissue-residency program that limits their contribution to tumor control and ICB response. By contrast, MYB-dependent stem-like TPEX cells residing in tdLNs sustained CD8+ T cell infiltration into tumors and mediated ICB response. The cytokine TGFβ was the central factor that enforced residency of intratumoral CD8+ T cells and limited the abundance of stem-like TPEX cells in tdLNs, thereby restraining tumor control. A similar network of TGFβ-constrained intratumoral and extratumoral CD8+ T cells with precursor and residency characteristics was found in human cancer.
    DOI:  https://doi.org/10.1038/s41590-025-02219-2
  10. Nat Protoc. 2025 Jul 25.
    Manufacturing of CRISPR-edited primary mouse CAR T cells for cancer immunotherapy.
    Puneeth Guruprasad, Ranjani Ramasubramanian, Siena Nason, Alberto Carturan, Shan Liu, Luca Paruzzo, Vladlena Hornet, Jacqueline Plesset, Ruchi P Patel, Vijay Bhoj, Gregory L Beatty, Marco Ruella.
      Editing chimeric antigen receptor (CAR) T cells by using CRISPR-Cas9 has become a routine strategy to improve their antitumor function or safety profile. Xenograft tumor models in immunodeficient mice are often used to evaluate the function of CRISPR-edited human CAR T cells. These models, however, lack functional immune systems and thus fail to recapitulate barriers such as the immunosuppressive tumor microenvironment (TME) that CAR T cells will encounter in patients. Thus, genetically modifying mouse CAR T cells for use in immune-intact models is an attractive approach to explore the impact of a given gene deletion on CAR T cells within a natural TME. Here, we describe a protocol to perform CRISPR-Cas9 editing in primary mouse T cells, thereby enabling studies of gene-edited CAR T within the TME and in the presence of a functional immune system. This protocol is integrated into a standard mouse CAR T manufacturing workflow, a process that typically spans ~5-6 days. The first stage of this protocol involves isolating mouse T cells, electroporating them with a ribonucleoprotein complex and activating them by using magnetic bead stimulation. The second stage involves transducing the CAR gene and expanding these cells, and the third stage focuses on validating knockout efficiency and the functionality of gene-edited mouse CAR T cells. This procedure requires a proficiency in aseptic cell culture techniques and a basic understanding of T cell biology. We anticipate that efficient and reliable genetic modification of mouse T cells will have wide-ranging applications for cancer immunotherapies and related fields.
    DOI:  https://doi.org/10.1038/s41596-025-01208-x
  11. Biochem Biophys Res Commun. 2025 Jul 22. pii: S0006-291X(25)01105-2. [Epub ahead of print]778 152390
    Berberine alleviates T cell-driven lung inflammation by inhibiting cytokine secretion and regulating pulmonary microbiota.
    Ziqing Ma, Yu Zhou, Fudie Gu, Faji Wu, Yazhen Hong, Wen-Hsien Liu, Guangming Liu, Qingmei Liu, Chenfeng Liu.
      Berberine exhibits diverse biological activities including inhibition of T cell function to alleviate inflammatory diseases. However, the evidence and mechanisms by whether berberine directly regulates CD4+ T cells in vitro and in vivo remain unclear. Using an OVA-stimulated primary T cell activation model in vitro, berberine directly targeted T cells to suppress Th1 and Th17 differentiation. Moreover, berberine inhibited early T cell activation and proliferation while modestly promoting T cell apoptosis by downregulating Bcl2 expression. Mechanistically, transcriptomic analysis revealed that berberine controls the pro-inflammatory cytokine production by modulating JAK-STAT, PI3K/Akt, and NF-κB signals. Notably, inhibition of PTEN, a key negative regulator of these pathways, completely reversed the reduced cytokine release induced by berberine. In vivo experiments showed that berberine significantly improves pulmonary inflammation. In an OVA-specific T cell-mediated lung inflammation model, berberine markedly reduced activated CD4+ T cell infiltration and cytokine production in lung, as well as impaired their capacity to recruit other immune cells. Furthermore, berberine alters the social community and diversity of lung microbiota rather than inhibiting bacterial abundance, which potentially contribute to improved lung inflammation. Collectively, our findings elucidate the role and mechanisms of berberine in T cell differentiation and demonstrated its therapeutic effects in ameliorating lung inflammation through suppression of T cell function and modulation of pulmonary microbiota.
    Keywords:  Berberine; CD4(+) T cell differentiation; Cytokine production; Lung inflammation; Pulmonary microbiota
    DOI:  https://doi.org/10.1016/j.bbrc.2025.152390
  12. Trends Mol Med. 2025 Jul 24. pii: S1471-4914(25)00167-4. [Epub ahead of print]
    Host-microbe interactions in NAD+ metabolism.
    Xiaoyue Wu, Igor Shats, Xiaoling Li.
      Nicotinamide adenine dinucleotide (NAD+) is an essential cofactor for hundreds of biochemical reactions. Targeting NAD+ metabolism has been investigated as a therapeutic strategy for various metabolic, neurogenerative, and inflammatory conditions, including aging and cancer. Here we highlight recent advances in host-microbiome interactions regulating NAD+ metabolism and discuss their therapeutic potential.
    Keywords:  anticancer therapy; deamidated NAD(+) biosynthesis; dietary NAD(+) precursors; gut microbiota
    DOI:  https://doi.org/10.1016/j.molmed.2025.07.001
  13. Immunity. 2025 Jul 23. pii: S1074-7613(25)00311-5. [Epub ahead of print]
    Innate-like memory T cells rapidly emerge in humans after gene therapy for SCID-X1 test.
    Anoop Babu Vasandan, Hossam A Abdelsamed, Shannon K Boi, Grace Ward, Shanta Alli, Tian Mi, Xin Lan, Xusheng Zhang, Morton J Cowan, Jennifer M Puck, Aleksandra Petrovic, David Rawlings, Albert Zhou, Ewelina Mamcarz, Stephen Gottschalk, Caitlin C Zebley, Ben Youngblood.
      Virtual memory T cells, possessing features of innate immune cells, represent a developmental continuum between innate and adaptive immunity. Here, we describe the genesis of virtual memory T cells during early human life. A longitudinal analysis of peripheral T cells after gene therapy for X-linked severe combined immunodeficiency (SCID-X1) in infants revealed an early enrichment of innate-like memory CD8+ T cells that expressed NKG2A, innate-associated transcriptional profiles, and a distinct T cell receptor (TCR) repertoire. Genome-wide DNA methylation profiling of the de novo innate-like memory NKG2A+ T cell subset confirmed a subset-specific epigenetic signature that included a poised effector response. Furthermore, ex vivo stimulation of NKG2A+ T cells with IL-12 and IL-18 resulted in antigen-independent interferon gamma (IFNγ) expression. Collectively, these data indicate that NKG2A+ innate-like memory T cells develop early in human life and are epigenetically poised to rapidly elicit effector cytokines in an antigen-independent manner.
    Keywords:  human immune development; innate-memory T cells; virtual memory T cells
    DOI:  https://doi.org/10.1016/j.immuni.2025.07.002
  14. J Allergy Clin Immunol. 2025 Jul 28. pii: S0091-6749(25)00806-1. [Epub ahead of print]
    CARMIL2 deficiency disrupts activation-induced metabolic reprogramming in T cells, and is partially rescued by glutamine supplementation.
    Mona Kabha, Maya Liaks-Bohnick, Fadia Zagairy, Orna Atar, Mira Hamed, Michael Ziv, Nada Danial-Farran, Morad Khayat, Orly Ishach, Yael Dinur-Schejter, Vered Molho-Pessach, Ido Somekh, Shirly Frizinsky, Efrat Bar-Ilan, Shoshana Greenberger, NaserEddin Adeeb, Raz Somech, Polina Stepansky, Noga Ron-Harel, Eran Cohen-Barak.
       BACKGROUND: T-cell activation requires signaling through the T-cell receptor and costimulatory molecules, including CD28, triggering metabolic reprogramming to support growth and proliferation of the activating T -cell. CARMIL2, a scaffold protein, facilitates CD28-mediated signaling. Individuals with CARMIL2 mutations experience inborn errors of immunity, leading to T-cell dysfunction and severe infectious and inflammatory comorbidities. However, how CARMIL2 deficiency impacts T cell metabolic reprogramming remains unknown.
    OBJECTIVE: To investigate how CARMIL2 deficiency affects activation-induced metabolic reprogramming in T-cells.
    METHODS: CD4+ T-cells were isolated from patients with CARMIL2 deficiency and matched healthy controls (HC). Transcriptomic profile was analyzed by bulk RNA sequencing and whole-cell metabolomics by liquid chromatography-mass spectrometry (LC-MS/MS). Activation markers and signaling pathways were measured by flow cytometry. These approaches informed identification of specific amino acids for rescue experiments.
    RESULTS: Nine patients with CARMIL2 deficiency and sixteen age-and sex-matched healthy controls were recruited. RNA sequencing of CD4+ T-cells revealed decreased expression of genes associated with metabolic activity, including mTOR signaling, glycolysis, one-carbon metabolism, and glutamine metabolism. Whole cell metabolomics reinforced these results and highlighted glutamine deficiency as a potential driver of the observed metabolic phenotype. Glutamine supplementation restored NF-kB and mTOR activity, as measured by p-65 and RPS phosphorylation, respectively, and upregulated the expression of IL17A in CARMIL2-mutated CD4+ T cells.
    CONCLUSIONS: CARMIL2 deficiency disrupts T-cell metabolic reprogramming and was partially rescued ex-vivo with glutamine supplementation. These findings highlight a potential therapeutic approach targeting metabolism to improve immune function in individuals with CARMIL2 deficiency.
    Keywords:  CARMIL2; Glutamine; Metabolism; T -cell; mTOR
    DOI:  https://doi.org/10.1016/j.jaci.2025.07.018
  15. Sci Immunol. 2025 Aug;10(110): eadv0985
    CD4 T cell therapy counteracts inflammaging and senescence by preserving gut barrier integrity.
    Manuel M Gómez de Las Heras, Elisa Carrasco, Mario Pérez-Manrique, Naohiro Inohara, Sandra Delgado-Pulido, Álvaro Fernández-Almeida, María I Gálvez-Castaño, Isaac Francos-Quijorna, Carolina Simó, Virginia García-Cañas, José Ignacio Escrig-Larena, Juan Francisco Aranda, Gonzalo Soto-Heredero, Enrique Gabandé-Rodríguez, Eva María Blanco, Joyce Días-Almeida, Gabriel Núñez, María Mittelbrunn.
      Healthy aging relies on a symbiotic host-microbiota relationship. The age-associated decline of the immune system can pose a threat to this delicate equilibrium. In this work, we investigated how the functional deterioration of T cells can affect host-microbiota symbiosis and gut barrier integrity and the implications of this deterioration for inflammaging, senescence, and health decline. Using the Tfamfl/flCd4Cre mouse model, we found that T cell failure compromised gut immunity leading to a decrease in T follicular cells and regulatory T cells (Treg cells) and an accumulation of highly proinflammatory and cytotoxic T cells. These alterations were associated with intestinal barrier disruption and gut dysbiosis. Microbiota depletion or adoptive transfer of total CD4 T cells or a Treg cell-enriched pool prevented gut barrier dysfunction and mitigated premature inflammaging and senescence, ultimately enhancing the health span in this mouse model. Thus, a competent CD4 T cell compartment is critical to ensure healthier aging by promoting host-microbiota mutualism and gut barrier integrity.
    DOI:  https://doi.org/10.1126/sciimmunol.adv0985
  16. Eur J Immunol. 2025 Aug;55(8): e70011
    Spatial Organisation of Tumour cDC1 States Correlates with Effector and Stem-Like CD8+ T Cells Location.
    Cécile Piot, Mariana Pereira da Costa, Adi Biram, Carlos M Minutti, Kok Haw Jonathan Lim, Mary Green, Ania Mikolajczak, Robert P Jenkins, Lucy Meader, Michael D Buck, Ana Cardoso, Neil Rogers, Erik Sahai, Caetano Reis E Sousa.
      CD8+ T cells are central to targeting and eliminating cancer cells. Their function is critically supported by type 1 conventional dendritic cells (cDC1s), which both prime antigen-specific CD8+ T cells in tumour-draining lymph nodes (tdLNs) and sustain primed CD8+ T cells within tumours. Despite their importance, the spatiotemporal organisation of cDC1s within tumours and their diverse functional roles remain poorly understood. Here, we use scRNAseq and unbiased spatial analysis to construct a detailed map of cDC1 states and distribution within immunogenic mouse tumours during CD8+ T-cell-mediated rejection. We reveal two distinct cDC1 activation states characterised by differential expression of genes linked to anti-tumour immunity, including Cxcl9 and Il12b. Strikingly, Il12b-expressing cDC1s are CCR7+ and enriched at tumour borders, where they closely associate with stem-like TCF1+ CD8+ T cells. In contrast, CCR7- Cxcl9-expressing cDC1s are preferentially found within the tumour parenchyma alongside effector CD8+ T cells. Analysis of a published dataset of human tumours similarly reveals a spatial association between CCR7+ cDC1 and stem-like TCF1+ CD8+ T cells. These findings uncover a highly spatially coordinated interaction between cDC1s and CD8+ T cells within tumours, shedding light on the intricate cellular dynamics that underpin effective anti-tumour immunity.
    Keywords:  CD8 T cells; dendritic cells; spatial; tumour immunology
    DOI:  https://doi.org/10.1002/eji.70011
  17. Curr Allergy Asthma Rep. 2025 Jul 26. 25(1): 31
    CD8+ T Cells You Should Know about in Autoimmunity: Current Paradigms of T Cell Pathogenesis in Autoimmune Disease.
    Laura Lim, Anna Helena Jonsson.
       PURPOSE OF REVIEW: CD8 T cells comprise a large portion of cells in inflamed tissues in many autoimmune diseases, yet their roles in autoimmune pathogenesis have been unclear.
    RECENT FINDINGS: Newer studies have demonstrated that CD8 T cells perform many effector functions that may play a vital role in autoimmune disease pathogenesis. In some autoimmune diseases, such as type 1 diabetes and polymyositis, classical cytotoxic T lymphocytes are thought to play a driving role, but in most tissues affected by autoimmune disease, granzyme K-expressing CD8 T cells are the most abundant. These cells have low cytotoxic potential and instead stimulate nearby cells by releasing cytokines and granzyme K, which can activate complement cascades. Resident memory CD8 T cells are also present in autoimmune tissues, although their roles in pathogenesis are less clear. Foxp3+ CD8 T cells exist, but regulatory functions of CD8 T cells extend beyond this population, as CD39 and GzmB expressed by other CD8 T cell subsets can suppress or kill nearby antigen-presenting cells and other pro-inflammatory cells. In this review, we describe CD8 T cell subsets and functions, their associations with human autoimmune diseases, as well as current and in-development treatments that target CD8 T cells.
    Keywords:  Autoimmune Disease; CD8 T cells; Granzyme B; Granzyme K; Human immunology; Resident memory T cells
    DOI:  https://doi.org/10.1007/s11882-025-01211-y
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