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CCR2- T peripheral helper cells as potential coordinators of local immune architecture in human cancer. CCR2- T外周辅助细胞作为人类癌症局部免疫结构的潜在协调者。
Discovery immunology Pub Date : 2026-03-23 eCollection Date: 2026-01-01 DOI: 10.1093/discim/kyag007
Celia Del Carmen Crespo Oliva, Zoé Gerber, Dominique Jean, Hugues Allard-Chamard, Marilyne Labrie
{"title":"CCR2<sup>-</sup> T peripheral helper cells as potential coordinators of local immune architecture in human cancer.","authors":"Celia Del Carmen Crespo Oliva, Zoé Gerber, Dominique Jean, Hugues Allard-Chamard, Marilyne Labrie","doi":"10.1093/discim/kyag007","DOIUrl":"https://doi.org/10.1093/discim/kyag007","url":null,"abstract":"<p><strong>Introduction: </strong>Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, yet tumor progression remains a challenge, necessitating improved patient stratification and therapeutic strategies. Tumor growth releases neoantigens that activate adaptive immunity, promoting tertiary lymphoid structure (TLS) formation through B- and T-cell interactions. T follicular helper (Tfh) cells are key in coordinating B-cell responses and are linked to favorable outcomes. A newer subset, T peripheral helper (Tph) cells, shares functional traits with Tfh cells but differs in transcriptional and migratory profiles. Though observed in various cancers, their distribution and role in tumor immunity are not fully understood.</p><p><strong>Methods: </strong>To investigate this, a multiplex cyclic immunofluorescence assay was developed to detect and spatially analyze Tph cells in tumors.</p><p><strong>Results: </strong>This revealed three CXCL13-expressing CD4<sup>+</sup> T-cell subsets: Tfh, Tph, and a 'C-C motif chemokine receptor 2 (CCR2)<sup>-</sup> Tph-like' population which, in contrast to the classically CCR2-enriched Tph phenotype described in inflamed tissues, shows markedly reduced CCR2 expression. Downregulation of CXCR5 and CCR2 near CCR2<sup>-</sup> Tph-like cells suggested a shift toward local immune residency, forming immune niches. These niches were enriched with pro-inflammatory cells, including Th1, Th17, CD4<sup>+</sup>, CD8<sup>+</sup> T cells, and B cells. Spatial profiling showed CCR2<sup>-</sup> Tph-like cells embedded in an immunoregulatory network, marked by CD69 and inhibitory checkpoints B7-H3 and PD-L1 on surrounding cells.</p><p><strong>Conclusions: </strong>This dual signaling suggests CCR2<sup>-</sup> Tph-like cells may modulate tumor immunity by balancing activation and suppression, with potential implications for checkpoint blockade therapy.</p>","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"5 1","pages":"kyag007"},"PeriodicalIF":0.0,"publicationDate":"2026-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13058833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147647583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction to: Inflammation's impact on the interaction between oligodendrocytes and axons. 更正:炎症对少突胶质细胞和轴突之间相互作用的影响。
Discovery immunology Pub Date : 2026-03-07 eCollection Date: 2026-01-01 DOI: 10.1093/discim/kyag005
{"title":"Correction to: Inflammation's impact on the interaction between oligodendrocytes and axons.","authors":"","doi":"10.1093/discim/kyag005","DOIUrl":"10.1093/discim/kyag005","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/discim/kyaf008.].</p>","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"5 1","pages":"kyag005"},"PeriodicalIF":0.0,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12967065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147379688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Out of the shed and into the field: an immune toolkit for measuring wild ungulate immune phenotypes at multiple scales. 走出棚子,走进田野:一个免疫工具包,用于在多个尺度上测量野生有蹄类免疫表型。
Discovery immunology Pub Date : 2026-03-05 eCollection Date: 2026-01-01 DOI: 10.1093/discim/kyag001
Luke Weinstein, Brian P Dolan, Holly K Arnold, Sara Carpenter, Leigh Combrink, Clinton W Epps, Jennifer L Johns, Emma Lantz, Brandon Munk, Shannon Phelps, Paige Prentice, Nicholas Shirkey, Marci Witczak, Anna E Jolles, Brianna R Beechler
{"title":"Out of the shed and into the field: an immune toolkit for measuring wild ungulate immune phenotypes at multiple scales.","authors":"Luke Weinstein, Brian P Dolan, Holly K Arnold, Sara Carpenter, Leigh Combrink, Clinton W Epps, Jennifer L Johns, Emma Lantz, Brandon Munk, Shannon Phelps, Paige Prentice, Nicholas Shirkey, Marci Witczak, Anna E Jolles, Brianna R Beechler","doi":"10.1093/discim/kyag001","DOIUrl":"10.1093/discim/kyag001","url":null,"abstract":"<p><strong>Introduction: </strong>Understanding factors that shape immune responses in wild animals is critical to predicting population resilience and long-term persistence. Immune function modifies the survival of individuals facing infectious disease, trauma, and environmental stressors, yet remains understudied. An individual's immune response is shaped not only by current and historic pathogen exposures but is mediated by both individual (e.g. host genetics, metabolic plane, age, and sex) and population-level (e.g. population size, density, and connectivity) factors. Bighorn sheep (<i>Ovis canadensis</i>, bighorn) occupy populations of varying sizes, nested within larger metapopulations, creating a hierarchical structure. This organization provides a useful framework to understand how immune parameters vary across individual, population, and metapopulation levels. Unfortunately, measurement of immune parameters in ungulates is limited.</p><p><strong>Methods: </strong>To address this limitation, we measured 18 immunologic traits across 581 wild bighorn to evaluate this toolkit's ability to detect immunological differences between individuals, populations, and metapopulations.</p><p><strong>Results: </strong>Most immunological phenotypes illustrated significant variation at the metapopulation level and individual level. Our assays revealed immune phenotypic variation consistent with two main axes of segregation-one that distinguished tradeoffs in bighorn innate versus adaptive immune responses, and another reflecting alternative inflammatory states, defined by distinct cytokine patterns. Bighorn age and sex also mediated immune response patterns.</p><p><strong>Conclusions: </strong>Our immunological toolkit sets the stage to further clarify landscape-level immunological variation in wild ungulate populations and provides a template for deploying integrative eco-immunological tools in any natural population to further understand wildlife health.</p>","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"5 1","pages":"kyag001"},"PeriodicalIF":0.0,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12961423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147379716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Porcine influenza mAbs to H3, H5, and H7 hemagglutinins recognize H3 egg adapted site and target the HA stem. 针对H3、H5和H7血凝素的猪流感单抗识别H3卵适应位点并靶向血凝素干细胞。
Discovery immunology Pub Date : 2026-03-02 eCollection Date: 2026-01-01 DOI: 10.1093/discim/kyag006
Tiphaine Cayol, Sonia Villanueva-Hernández, Emily Briggs, Charlotte May, Adam McNee, Ashutosh Vats, Bharti Mittal, Jean-Remy Sadeyen, Munir Iqbal, Danish Munir, Marie Di Placido, John A Hammond, Alain Townsend, Pramila Rijal, Basudev Paudyal, Elma Tchilian
{"title":"Porcine influenza mAbs to H3, H5, and H7 hemagglutinins recognize H3 egg adapted site and target the HA stem.","authors":"Tiphaine Cayol, Sonia Villanueva-Hernández, Emily Briggs, Charlotte May, Adam McNee, Ashutosh Vats, Bharti Mittal, Jean-Remy Sadeyen, Munir Iqbal, Danish Munir, Marie Di Placido, John A Hammond, Alain Townsend, Pramila Rijal, Basudev Paudyal, Elma Tchilian","doi":"10.1093/discim/kyag006","DOIUrl":"10.1093/discim/kyag006","url":null,"abstract":"<p><strong>Introduction: </strong>Monoclonal antibodies (mAbs) are critical tools for elucidating viral evolution, informing vaccine design, and developing antiviral therapeutics. Large-animal models, such as the pig, that closely mirror human immune responses are essential for understanding influenza immunity.</p><p><strong>Methods: </strong>Pigs were either infected or sequentially immunized with influenza viruses and monoclonal antibodies directed against H3, H5, and H7 influenza virus haemagglutinins were isolated. Antibody specificity, breadth, epitope targeting (head versus stem), neutralizing capacity, and Fc-mediated activity were assessed across influenza subtypes.</p><p><strong>Results: </strong>Pigs generated both strain-specific and broadly reactive mAbs targeting haemagglutinin head and stem epitopes. An H3-specific mAb (H3-57) selectively recognized the egg-adapted L194P mutation associated with reduced human vaccine effectiveness. H5 and H7 immunization induced neutralizing antibodies, including cross-group stem mAbs reactive with H1, H3, and H5 haemagglutinins. Fc-mediated activity correlated with antibody binding strength rather than epitope location.</p><p><strong>Conclusions: </strong>These findings demonstrate that pigs mount antibody responses closely resembling those observed in humans, including recognition of conserved stem epitopes and adaptive head mutations. Porcine mAbs represent powerful new tools for dissecting influenza immunity, guiding vaccine design, and enhancing pandemic preparedness using a physiologically relevant large-animal model.</p>","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"5 1","pages":"kyag006"},"PeriodicalIF":0.0,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13006140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147505512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Immunity to helminths in complex environments: co-infection disrupts effective granuloma formation and parasite clearance. 在复杂环境中对蠕虫的免疫:共同感染破坏有效的肉芽肿形成和寄生虫清除。
Discovery immunology Pub Date : 2026-02-28 eCollection Date: 2026-01-01 DOI: 10.1093/discim/kyag004
Breton Fougere, Anupama Ariyaratne, Naomi Chege, Shashini Perera, Emma Forrester, Jyrus Capara, Aralia Leon Coria, Mayara de Cassia Luzzi, Joel Bowron, Edina K Szabo, Constance A M Finney
{"title":"Immunity to helminths in complex environments: co-infection disrupts effective granuloma formation and parasite clearance.","authors":"Breton Fougere, Anupama Ariyaratne, Naomi Chege, Shashini Perera, Emma Forrester, Jyrus Capara, Aralia Leon Coria, Mayara de Cassia Luzzi, Joel Bowron, Edina K Szabo, Constance A M Finney","doi":"10.1093/discim/kyag004","DOIUrl":"10.1093/discim/kyag004","url":null,"abstract":"<p><strong>Introduction: </strong>The intestinal roundworm <i>Heligmosomoides bakeri</i> establishes chronic infections in susceptible C57Bl/6 mice, yet repeated ('trickle') infections confer immunity and promote worm clearance. We previously linked this acquired immunity to enhanced intestinal granuloma formation. Here, we focused on effector molecules (antibodies) and cells (eosinophils and macrophages) known to immobilize and damage developing parasites.</p><p><strong>Methods and results: </strong>We used flow cytometry and immunofluorescence to show that granulomas in trickle-infected female mice contain elevated levels of IgG<sub>1</sub>, SiglecF<sup>+</sup> eosinophils and CD206<sup>+</sup> macrophages compared to bolus-infected animals, while IgG2c, IgA, and IgE were undetectable and levels of Ly6G<sup>+</sup> neutrophils or NK1.1<sup>+</sup> NK cells were unchanged. To mimic natural complexity, we introduced a mixed immune environment via prior <i>Toxoplasma gondii</i> infection which induces interferon-γ production in the small intestine. Co-infected mice exhibited fewer and smaller granulomas, which lacked IgG<sub>1</sub>, SiglecF<sup>+</sup> eosinophils, and CD206<sup>+</sup> macrophages, correlating with higher worm burdens.</p><p><strong>Conclusion: </strong>Together, these findings highlight the importance of local immune responses to tissue-invading worms and help explain why helminth elimination is frequently more difficult in the complex immune environments found in field settings compared with laboratory conditions.</p>","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"5 1","pages":"kyag004"},"PeriodicalIF":0.0,"publicationDate":"2026-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13006141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147505528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Large neutral amino acid uptake and mTOR activation within CD4 T cells coordinate type 2 immunity and host resistance to Trichuris muris. CD4 T细胞内大量中性氨基酸摄取和mTOR激活协调2型免疫和宿主对毛滴虫的抵抗。
Discovery immunology Pub Date : 2026-02-21 eCollection Date: 2026-01-01 DOI: 10.1093/discim/kyag003
Maria Z Krauss, Kelly S Hayes, Suzanne H Hodge, Ana Villegas-Mendez, Matthew R Hepworth, Linda V Sinclair, Kevin N Couper, Richard K Grencis
{"title":"Large neutral amino acid uptake and mTOR activation within CD4 T cells coordinate type 2 immunity and host resistance to <i>Trichuris muris</i>.","authors":"Maria Z Krauss, Kelly S Hayes, Suzanne H Hodge, Ana Villegas-Mendez, Matthew R Hepworth, Linda V Sinclair, Kevin N Couper, Richard K Grencis","doi":"10.1093/discim/kyag003","DOIUrl":"https://doi.org/10.1093/discim/kyag003","url":null,"abstract":"<p><strong>Introduction: </strong><i>Trichuris trichiura</i> (whipworm) is a gastrointestinal nematode that infects approximately 465 million people worldwide. <i>Trichuris muris</i> is used as a tractable model for the human whipworm. In wild-type mice, infection with a high dose of <i>T. muris</i> eggs leads to worm expulsion, which is dependent on a CD4Th2 response and interleukin (IL-)13 production. T cells up-regulate glycolysis and uptake of substrates following activation. The amino acid transporter SLC7A5 has been shown to be necessary for activation of mTORC1, a nutrient/energy/redox sensor critical for T cell differentiation into effector cells.</p><p><strong>Methods and results: </strong>We found that mice lacking SLC7A5 in CD4T cells have significantly delayed worm expulsion, associated with reduced IL-13, reduced pmTOR, and reduced glycolytic rates. However, as infection progressed, IL-13 levels recovered in T cell-specific SLC7A5-deficient mice, alongside resistance. The critical role of CD4T cell metabolism <i>per se</i> and downstream mTOR in CD4T cells in host resistance was shown in mice lacking mTOR in CD4T cells that failed to expel their parasites and developed chronic infection.</p><p><strong>Conclusion: </strong>Our study shows that mTOR is essential for optimal functioning of T cells during whipworm infection and that deletion of Slc7a5 significantly delays worm clearance indicating a key role for amino acid acquisition by CD4T cells in resistance to helminth infection.</p>","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"5 1","pages":"kyag003"},"PeriodicalIF":0.0,"publicationDate":"2026-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12971014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147437976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The T-cell receptor repertoire of wild mice. 野生小鼠的t细胞受体库。
Discovery immunology Pub Date : 2026-02-20 eCollection Date: 2026-01-01 DOI: 10.1093/discim/kyag002
Jacob A Cohen, Simon Hunter-Barnett, Gayathri Nageswaran, Suzanne Byrne, Gemma Freeman, Matthew V Cowley, Benny Chain, Mark Viney
{"title":"The T-cell receptor repertoire of wild mice.","authors":"Jacob A Cohen, Simon Hunter-Barnett, Gayathri Nageswaran, Suzanne Byrne, Gemma Freeman, Matthew V Cowley, Benny Chain, Mark Viney","doi":"10.1093/discim/kyag002","DOIUrl":"10.1093/discim/kyag002","url":null,"abstract":"<p><strong>Introduction: </strong>Wild animals live in a pathogen-rich environment and are normally infected with a wide range of micro- and macro-parasites. Wild animals' T cells are central to the effectiveness of their adaptive immune response in ameliorating the effect of these infections. Here, we have investigated the T-cell receptor (TCR) repertoire of wild mice to investigate how it varies in animals of different ages and sex and from different sites.</p><p><strong>Methods: </strong>We sequenced the TCR alpha and beta chains of CD4<sup>+</sup> and CD8<sup>+</sup> T cells of 65 wild <i>Mus musculus domesticus</i> from two UK sites.</p><p><strong>Results: </strong>We analysed repertoire richness and diversity finding that wild mice have large TCR repertoires. Repertoire richness, which measures the breadth of the repertoire, was not significantly affected by mouse age or sex, suggesting that wild mice maintain the capacity to respond to novel antigens throughout their lives. In contrast, repertoire diversity (measured by Shannon's index) was affected by a mouse sex-by-age interaction. This low diversity, coupled with constant richness, points to older mice having comparatively more highly abundant clones in their repertoires, perhaps due to chronic exposure to persistent pathogens in their environment.</p><p><strong>Discussion: </strong>These findings provide a novel description of the wild mouse TCR, revealing an immune system that balances maintaining a broad response capacity with developing strong, lasting responses to infections in the natural environment.</p>","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"5 1","pages":"kyag002"},"PeriodicalIF":0.0,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12994567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147482420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Striking a balance: how the gut microbiome shapes the fate of intestinal CD4+ T cells. 保持平衡:肠道微生物群如何塑造肠道CD4+ T细胞的命运。
Discovery immunology Pub Date : 2025-12-09 eCollection Date: 2026-01-01 DOI: 10.1093/discim/kyaf020
Jessica M Till, Orion D Brock, Philip P Ahern
{"title":"Striking a balance: how the gut microbiome shapes the fate of intestinal CD4+ T cells.","authors":"Jessica M Till, Orion D Brock, Philip P Ahern","doi":"10.1093/discim/kyaf020","DOIUrl":"10.1093/discim/kyaf020","url":null,"abstract":"<p><p>The induction of immune tolerance, a state of immunologic hyporesponsiveness to an antigen, is essential to prevent the destructive potential of the immune system in response to harmless or beneficial agents. Early efforts to understand tolerance focused on model stimuli, self-antigens, transplanted organs, and the growing fetus. Through co-evolution, the microbiome and the host immune system have developed strategies that promote immunological tolerance to the microbiome. This dialogue ensures the maintenance of mutualistic interactions that provide a stable habitat for the microbiome which in turn confers numerous physiological benefits to the host. Despite the gut microbiome being a potent inducer of immune tolerance, the mechanisms through which specific members shaped immune function remained largely ignored for decades. The growing appreciation for the immunomodulatory capacity of the microbiome has led to a massive expansion of efforts to define how the balance between tolerance and inflammation is induced and maintained at mucosal sites like the intestine. While the ensuing research uncovered myriad fundamental insights into the concerted host and microbial functions promoting host-microbiome mutualism, inducing tolerance to clinically relevant antigens remains a major challenge in the development of tolerogenic therapies. Here, we trace the interaction between intestinal CD4+ T cells and the microbiome, from antigen uptake through to the development of a polarized collection of CD4+ T cells, whose functions are essential for immunological tolerance, and highlight the knowledge gaps that limit efforts to leverage these interactions for clinical benefit.</p>","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"5 1","pages":"kyaf020"},"PeriodicalIF":0.0,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12880901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146144793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Evidence for a RIPK1-independent survival mechanism for CASPASE-8 in αβ T cells. CASPASE-8在αβ T细胞中独立于ripk1存活机制的证据。
Discovery immunology Pub Date : 2025-11-28 eCollection Date: 2025-01-01 DOI: 10.1093/discim/kyaf016
Farjana Islam, Scott Layzell, Ines Boal-Carvalho, Benedict Seddon
{"title":"Evidence for a RIPK1-independent survival mechanism for CASPASE-8 in αβ T cells.","authors":"Farjana Islam, Scott Layzell, Ines Boal-Carvalho, Benedict Seddon","doi":"10.1093/discim/kyaf016","DOIUrl":"10.1093/discim/kyaf016","url":null,"abstract":"<p><strong>Introduction: </strong>CASPASE8 promotes both cell death and survival by acting as a trigger of apoptosis and a repressor of necroptosis. In T cells, the function and mechanisms of CASPASE8 are incompletely understood.</p><p><strong>Methods: </strong>Here, we analysed mice in which <i>Casp8</i> was conditionally deleted in T cells at different stages of development.</p><p><strong>Results: </strong>In mice with deletion early in T cell development, we observed a modest reduction in early thymic progenitors and a striking absence of NKT cells in the thymus. Amongst mature peripheral T cells, there was a substantial and specific reduction in the CD8 T cell compartment, which included naive, central memory and virtual memory subsets. Using a tamoxifen-inducible CD8<sup>CreERT</sup> to delete <i>Casp8</i> revealed an acute requirement for continued CASPASE8 expression for survival of a fraction of mature CD8 T cells. Analysing <i>Casp8-</i>deficient mice that express a kinase dead RIPK1 suggested that <i>in vivo</i>, necroptosis contributed to death of thymic progenitors and CD8EM and CD8CM subsets. However, kinase dead RIPK1 failed to restore NKT cell development or rescue the loss of CD4EM and CD4CM in mixed bone marrow chimeras, and only partially rescued CD8 VM T cell.</p><p><strong>Conclusions: </strong>Together, these observations suggest that CASPASE8 promotes T cell survival independent of its established role in repressing RIPK1-dependent necroptosis.</p>","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"4 1","pages":"kyaf016"},"PeriodicalIF":0.0,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12770974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145919396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Vaccination of calves with Bacille Calmette Guerin increased the frequency but did not affect aggregation or clustering of natural killer cells in draining lymph nodes. 小牛接种卡介苗增加了频率,但不影响自然杀伤细胞在引流淋巴结的聚集或聚集。
Discovery immunology Pub Date : 2025-11-13 eCollection Date: 2025-01-01 DOI: 10.1093/discim/kyaf017
Jayne C Hope, Sarah Ho, Clara Zifko, Carly A Hamilton, Darren J Shaw
{"title":"Vaccination of calves with Bacille Calmette Guerin increased the frequency but did not affect aggregation or clustering of natural killer cells in draining lymph nodes.","authors":"Jayne C Hope, Sarah Ho, Clara Zifko, Carly A Hamilton, Darren J Shaw","doi":"10.1093/discim/kyaf017","DOIUrl":"10.1093/discim/kyaf017","url":null,"abstract":"<p><strong>Introduction: </strong>Natural killer (NK) cells are central to innate immune responses but they also influence adaptive immunity. Evidence suggests that NK cells are involved in protective immune responses induced by the Bacille Calmette Guerin (BCG) vaccine. In cattle, vaccination with BCG provides significant protection against infection with <i>Mycobacterium bovis</i>, the causative agent of bovine tuberculosis (bTB). Bovine NK cells were previously shown to traffic from BCG vaccination sites in afferent lymph, and to be activated reciprocally through interactions with dendritic cells (DC) to drive high-level interferon gamma secretion. To further define roles for bovine NK cells in the induction of BCG vaccine-mediated immunity, we examined alterations in their frequency, location, and aggregation in lymph nodes (LN) draining immunization sites.</p><p><strong>Materials and methods: </strong>Calves were either not vaccinated, vaccinated with BCG once, or were re-vaccinated. The frequency and localization of NK cells in draining LN was examined by immunohistochemistry and immunofluorescence, and statistical analyses of imaging outputs were performed.</p><p><strong>Results: </strong>While increased numbers of NK cells were found in BCG-draining LN, there were no significant alterations in location, nor the clustering or aggregation of NK cells. Re-vaccination with BCG had little impact on NK cell numbers or location.</p><p><strong>Conclusion: </strong>BCG vaccination induced changes in NK cell frequency in bovine LN. Further studies of NK cell function and co-localization with subsets of DC and T cells will be important to define the roles of these cells in the induction of protective immunity in bTB.</p>","PeriodicalId":72830,"journal":{"name":"Discovery immunology","volume":"4 1","pages":"kyaf017"},"PeriodicalIF":0.0,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12772509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145918960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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