Clinical & Translational Immunology最新文献

{"title":"Enhancing CAR T-cell therapy manufacturing efficiency through semi-automated bioprocessing","authors":"Jason Isaacson, Prajakta Bhanap, Nicholas Putnam, Jasmine Padilla, Nujhat Fatima, Max Dotson, Danny Hayoun, Moloud Ahmadi, Gertrude Nonterah, Yongchang Ji","doi":"10.1002/cti2.70025","DOIUrl":"https://doi.org/10.1002/cti2.70025","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Chimeric antigen receptor (CAR) T-cell therapies have revolutionised the treatment of blood-based malignancies. The use of manual CAR T-cell manufacturing methods is one of the challenges that contributes to these delays. As CAR T therapy emerges as a potential first- or second-line treatment option for these cancers, the demand for these therapies continues to rise. However, challenges persist in ensuring that the patients who need these therapies receive them in a timely manner. Automated CAR T-cell manufacturing methods that use software to control the equipment used in the process can help overcome the roadblocks associated with manual manufacturing, ultimately enabling a reduction in variability, increased efficiency, improved product quality and better data management. This paper aims to present an end-to-end semi-automated methodology for manufacturing CAR T cells using the Cell Therapy Systems (CTS™) Cellmation software – an off-the-shelf software solution – to control physically connected modular cell therapy instruments that eliminates the roadblocks associated with manual manufacturing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>T cells from healthy donors were isolated and processed into CAR T cells using a semi-automated, connected, multi-instrument setup that leveraged electroporation and a CRISPR/Cas system for delivering the CD19-CAR construct to the T cells. Flow cytometry was used to assess cell type composition, cell viability and expression of T-cell activation markers throughout the process. We also measured exhaustion marker expression on T cells, T-cell receptor (TCR) knock-out, CAR knock-in and cytotoxic activity against NALM6 cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The results demonstrated the successful generation of functional CAR T cells using a semi-automated instrument workflow. The results were similar to the results from CAR T cells manufactured using non-automated processes; however, the successful connection and control of the instruments using automated software present an exciting opportunity for process developers and manufacturers who want to reduce manual touchpoints in their cell therapy manufacturing process.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The method that we describe in this paper could be beneficial to process development and manufacturing teams that might require flexibility in their CAR T cell manufacturing workflow and want to take advantage of modular systems that can be automated using the Cellmation software to reduce the proble","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 6","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144197100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Data standards for single-cell RNA-sequencing of paediatric cancer","authors":"Xiaohan Xu,&nbsp;John Saxon,&nbsp;Megan Sioe Fei Soon,&nbsp;Colin YC Lee,&nbsp;Zewen Kelvin Tuong","doi":"10.1002/cti2.70033","DOIUrl":"https://doi.org/10.1002/cti2.70033","url":null,"abstract":"<p>Single-cell RNA sequencing (scRNA-seq) is a powerful tool for investigating paediatric cancers, but individual studies often profile a small number of individuals. It is now the standard practice to upload the scRNA-seq data to data repositories to support scientific reproducibility. Public data deposition is a cost-effective and sustainability-conscious solution that allows any researcher to download and analyse existing scRNA-seq data to develop new ideas. This is incredibly valuable, especially in the context of paediatric cancer research, where access to funding and to patient cohorts may be prohibitive. However, standards for data deposition are absent, leading to significant issues that may slow progress. As a consequence, it is difficult, even impossible, for other researchers to validate findings or utilise these data for tailored analyses. Here, we systematically accessed and reviewed publicly available scRNA-seq data sets from various paediatric cancer studies, covering over 1.3 million cells across 488 clinical samples. We highlight striking inconsistencies with study design and data availability across several levels, which hinder downstream analyses and data reproducibility. To address these challenges, we propose a recommendations framework to improve data deposition practices that promote more effective use of scRNA-seq data sets deposited on public repositories and accelerate discoveries in paediatric cancer research and beyond. We urge data standards institutes and repositories, such as NCBI Gene Expression Omnibus (GEO) and European Genome-Phenome Archive (EGA), to strictly enforce these standardised data practices.</p>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 5","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-dimensional flow cytometry reveals lymphocyte subset populations predictive of chronic lung allograft dysfunction","authors":"Rohia Farighi,&nbsp;Steven Hiho,&nbsp;Thomas Ashhurst,&nbsp;Emily SJ Edwards,&nbsp;Lucy Sullivan,&nbsp;Menno C van Zelm,&nbsp;Greg Snell,&nbsp;Glen Westall,&nbsp;David M Tarlinton,&nbsp;Dimitra Zotos","doi":"10.1002/cti2.70035","DOIUrl":"https://doi.org/10.1002/cti2.70035","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Despite cellular and antibody-mediated rejection being clinically relevant drivers of chronic lung allograft dysfunction (CLAD), there are few studies describing the T- and B-cell dynamics inherent to such alloreactive responses. We conducted a longitudinal immunophenotyping study of B- and T-cell subsets from pre- to 12 months post-lung transplant, focussing on patients who subsequently developed either donor specific antibodies to human leukocyte antigen class II (HLA-DSA) or CLAD within 3 years.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In a single centre, comparative study, we used high-dimensional flow cytometry clustering analysis to assess the B- and T-cell populations in blood from lung allograft recipients prior to transplantation and at 0.5, 1.5, 3, 6, 9 and 12 months post-transplantation. Recipients who developed <i>de novo</i> HLA-DSA at 3 months post-transplantation (<i>n</i> = 18) and those in whom CLAD was diagnosed within 3 years post-transplantation (<i>n</i> = 13) were compared to matched, DSA-negative (<i>n</i> = 15) or CLAD-free recipients (<i>n</i> = 26), respectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>This longitudinal study provided a detailed analysis of B- and T-cell lineage subsets, including both cell frequencies and cell counts. There were no statistically significant differences in lymphocyte populations between graft recipients with and without HLA-DSA. However, patients that developed CLAD had a mean threefold deficit in the absolute number of B cells and had significantly fewer T regulatory cells than CLAD-free patients. Strikingly, these differences existed prior to and persisted post-transplantation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Utilising high-dimensional flow cytometry, a new putative association was identified between two peripheral blood lymphocyte populations and the subsequent development of CLAD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 5","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70035","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144126086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antigen-specific polyfunctional cytotoxic T cells differentiate intraocular from peripheral blood immune responses in posterior uveitis","authors":"Kaiser Alam,&nbsp;Arun Raina,&nbsp;Bibhuprasad Das,&nbsp;Sandhya Bhanja,&nbsp;Sayantan Ghosh,&nbsp;John V Forrester,&nbsp;Soumyava Basu","doi":"10.1002/cti2.70036","DOIUrl":"https://doi.org/10.1002/cti2.70036","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Peripheral blood is frequently used to study the immune response in human uveitis because of the inaccessibility of ocular tissue samples. To determine whether peripheral blood immune cells accurately reflect the intraocular immune response, we compared the T-cell profiles and antigen-specific cytokine responses between paired vitreous and peripheral blood samples from patients with sight-threatening posterior uveitis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We collected paired vitreous and peripheral blood mononuclear cells (PBMCs) from 24 patients with posterior uveitis. Multi-parametric flow cytometry was employed to identify surface and intracellular cytokine markers after activation with candidate antigenic peptides [<i>Mycobacterium tuberculosis</i> (MTb) peptides and retinal autoantigens]. Data were analysed through manual gating, unsupervised clustering and dimensionality reduction (FlowSOM, FlowJo).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The CD8⁺/CD4⁺ ratio in a representative set of seven paired samples was higher in the vitreous than in PBMCs. Vitreous CD4⁺ and CD8⁺ cells displayed greater polyfunctional potential (TNFα⁺IFNγ⁺IL-2⁺ and PMA/ionomycin activation) than PBMCs. Upon antigen-specific activation <i>in vitro</i>, vitreous CD8⁺ T cells (but not CD4⁺ T cells) showed a stronger polyfunctional response than PBMCs against both MTb (in TB-immunoreactive patients) and retinal autoantigens. Unsupervised clustering identified 15 distinct CD3⁺ T-cell metaclusters, each with unique profiles in the vitreous and PBMCs. Significant cluster enrichment was observed among the vitreous infiltrating cells in TB-immunoreactive cases compared to non-TB uveitis, but no such enrichment was found among PBMCs in either patient cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The vitreous T-cell compartment in this group of uveitis patients was functionally dominated by antigen-responsive cytotoxic CD8⁺ T cells and was distinct from the corresponding peripheral blood compartment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 5","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IgG promotes TNF-α induced osteoclastogenesis by upregulating the expression of TNFR1 and the NF-κB signalling pathway","authors":"Haifeng Yin,&nbsp;Yao Teng,&nbsp;Guo-Min Deng","doi":"10.1002/cti2.70034","DOIUrl":"https://doi.org/10.1002/cti2.70034","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Tumor necrosis factor-α (TNF-α) plays a pivotal role in bone damage associated with inflammatory arthritis such as rheumatoid arthritis (RA). Both systemic lupus erythematosus (SLE) and rheumatoid arthritis exhibit clinical manifestations of inflammatory arthritis, yet the joint bone damage in RA is more severe than that in SLE. The reasons for this differential manifestation remain unclear. This study aimed to determine the role of IgG antibodies in TNF-α-induced osteoclastogenesis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted cellular experiments to ascertain whether IgG affects TNF-α-induced osteoclastogenesis and validate the role of IgG in TNF-α-induced cartilage destruction in mouse models of arthritis through animal studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found that IgG promoted TNF-α-induced osteoclastogenesis by upregulating the expression of tumor necrosis factor receptor 1 (TNFR1) and enhancing the downstream nuclear factor-kappaB (NF-κB) signalling pathway. In the TNF-α-induced arthritis mouse model, IgG further exacerbated the destruction of articular cartilage.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings clarified that IgG aggravated TNF-α-mediated osteoclastogenesis, further elucidating the mechanistic basis for the divergent manifestations of joint bone damage in SLE and RA.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 5","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143914027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential reactivity of SARS-CoV-2 S-protein T-cell epitopes in vaccinated versus naturally infected individuals","authors":"Daniel J Browne,&nbsp;Pauline Crooks,&nbsp;Corey Smith,&nbsp;Denise L Doolan","doi":"10.1002/cti2.70031","DOIUrl":"https://doi.org/10.1002/cti2.70031","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Vaccine-induced protective immunity against SARS-CoV-2 has proved difficult to sustain. Robust T-cell responses are thought to play an important role, but T-cell responses against the SARS-CoV-2 spike protein (S-protein), the core vaccine antigen, following vaccination or natural infection are incompletely understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Herein, the reactivity of 170 putative SARS-CoV-2 S-protein CD8⁺ and CD4⁺ T-cell peptide epitopes in the same individuals prior to vaccination, after COVID-19 vaccination, and again following subsequent natural infection was assayed using a high-throughput reverse transcription-quantitative PCR (HTS-RT-qPCR) assay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The profile of immunoreactive SARS-CoV-2 S-protein epitopes differed between vaccination and natural infection. Vaccine-induced immunoreactive epitopes were localised primarily into two extra-domanial regions. In contrast, epitopes recognised following natural infection were spread across the antigen. Furthermore, T-cell epitopes in naïve individuals were primarily recognised in association with HLA-A, while natural infection shifted epitope associations towards HLA-B, particularly the B7 supertype.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study provides insight into T-cell responses against the SARS-CoV-2 S-protein following vaccination and subsequent natural infection.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 5","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70031","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143914026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Leveraging radiotherapy to improve immunotherapy outcomes: rationale, progress and research priorities","authors":"Faith Hartley,&nbsp;Martin Ebert,&nbsp;Alistair M Cook","doi":"10.1002/cti2.70030","DOIUrl":"https://doi.org/10.1002/cti2.70030","url":null,"abstract":"<p>The most successful immunotherapies for solid malignancies to date, immune checkpoint inhibitors, target the essential role of T cells in antitumor immunity. However, T-cell dysfunction presents a major hindrance to treatment efficacy, warranting research into combined treatment strategies for improving outcomes. The use of radiotherapy for this purpose has garnered much interest. Preclinical study has established that radiotherapy activates various immune mechanisms to improve T-cell activation, localisation and function within tumors, which improves response to immune checkpoint inhibitors. However, so far, these strategies have not been successfully translated into the clinic. Here, we briefly reflect on the development of immune checkpoint inhibitors and the mechanistic insights revealed by an evolving understanding of T-cell dysfunction in cancer, before providing an overview of the immunomodulatory effects of radiotherapy in the context of the T-cell-mediated antitumor immune response. We discuss the mixed results of clinical trials, comment on various factors that may preclude immuno-radiotherapy responses in the clinic, and highlight priorities for preclinical and clinical study. Finally, we discuss the role of emerging combinations of radiotherapy and immunotherapy to potentially provide additional treatment options and improve outcomes for patients.</p>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 4","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143793580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mucosal-associated invariant T cells correlate with myocardial ischaemia and remodelling in coronary artery disease","authors":"Jiafu Wang,&nbsp;Song Li,&nbsp;Xianling Zhou,&nbsp;Hongxing Wu,&nbsp;Xiaolan Ouyang,&nbsp;Zhuoshan Huang,&nbsp;Long Peng,&nbsp;Qian Chen,&nbsp;Yuman Wu,&nbsp;Zhitong Li,&nbsp;Ziyi Peng,&nbsp;Yi Yang,&nbsp;Yan Lu,&nbsp;Xixiang Tang,&nbsp;Yue Li,&nbsp;Suhua Li","doi":"10.1002/cti2.70029","DOIUrl":"https://doi.org/10.1002/cti2.70029","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Myocardial ischaemia and remodelling are major contributors to the progression and mortality of coronary artery disease (CAD). Previous studies have shown immune cell alterations in CAD patients, but their characteristics and associations with myocardial ischaemia and remodelling remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We compared immune cell changes among patients without CAD, those with CAD and those with CAD and heart failure (HF).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We found a progressive reduction in circulating mucosal-associated invariant T (MAIT) cells across the three patient groups. MAIT cells exhibited increased expression of activation markers (CD69 and PD-1) and cytotoxic molecules (such as granzyme B). The features of MAIT cells were correlated positively with worsening clinical indicators of myocardial ischaemia and remodelling, including the Gensini score, cTnI, NT-proBNP, LVEF and E/e′. Additionally, the reduction, activation and cytotoxicity of MAIT cells were associated with indicators of myocardial fibrosis (sST2, Gal-3, PICP and PIIINP), a central pathological mechanism of myocardial remodelling. Finally, we preliminarily explored potential triggers for MAIT cell abnormalities in CAD patients and found that impaired intestinal barrier function and increased circulating bacterial antigens may contribute to these changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>During CAD progression, we observed a decrease in circulating MAIT cells. Enhanced activation and cytotoxicity of MAIT cells are associated with myocardial ischaemia and remodelling in CAD patients with heart failure, potentially triggered by gut microbial leakage. Our findings suggest a novel strategy for monitoring and intervention in disease progression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 3","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70029","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"γδ T cell characterisation in the long term after haematopoietic stem cell transplantation and its impact on CMV control and cGVHD severity","authors":"Faisal Alagrafi,&nbsp;Arwen Stikvoort,&nbsp;Ahmed Gaballa,&nbsp;Martin Solders,&nbsp;Olle Ringden,&nbsp;Thomas Poiret,&nbsp;Lucas CM Arruda,&nbsp;Michael Uhlin","doi":"10.1002/cti2.70027","DOIUrl":"https://doi.org/10.1002/cti2.70027","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The clinical outcome after allogeneic haematopoietic stem cell transplantation (aHCT) relies greatly on the efficient recovery of T cells. Several studies have investigated the short-term γδ T cell reconstitution and their role in clinical outcomes following haematopoietic stem cell transplantation. Nevertheless, their long-term characteristics and impact have remained largely unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We analysed γδ T cells from 20 recipient/donor pairs at phenotypic, clonotypic and functional levels to assess their reconstitution ≥ 8 years (median 18 years) post-transplantation using high-parameter flow cytometry and next-generation sequencing of the TCR γ-chain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>γδ T cells displayed comparable phenotypic characteristics between recipients and matching donors. The Vδ2⁺ subset showed a more activated phenotype and cytokine production, while the Vδ1⁺ and non-Vδ2 T cells maintained long-term CMV control. TCR γ-chain composition in long-term survivors was largely restored, with no significant differences in gene segment usage or diversity. A small cohort of recipients with severe chronic graft-versus-host disease (GVHD) showed overrepresented donor-derived private clonotypes. Furthermore, we also found elevated HLA-DR⁺Vδ1⁺ T cells in recipients with severe chronic GVHD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Overall, γδ T cells reconstitute with a normalised repertoire, high functional capacity and sustained CMV control ability. An increased proportion of activated Vδ1⁺ T cells correlates with chronic GVHD severity, indicating a potential therapeutic target.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 3","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143565227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct MAIT cell phenotypes associated with sepsis clinical outcome in emergency department patients","authors":"Johanna Emgård,&nbsp;Iva Filipovic,&nbsp;Christian Unge,&nbsp;Laura M Palma Medina,&nbsp;Åsa Parke,&nbsp;Helena Bergsten,&nbsp;Kirsten Moll,&nbsp;Majda Dzidic,&nbsp;Helena Alpkvist,&nbsp;Hong Fang,&nbsp;Volkan Özenci,&nbsp;Niklas K Björkström,&nbsp;Mattias Svensson,&nbsp;Johan K Sandberg,&nbsp;Kristoffer Strålin,&nbsp;Anna Norrby-Teglund","doi":"10.1002/cti2.70028","DOIUrl":"https://doi.org/10.1002/cti2.70028","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Rapid diagnosis and intervention are critical for sepsis patient outcomes. However, diagnosis is challenging because of a heterogenic patient group as well as sometimes vague symptoms when the patient presents at the emergency department. Mucosal-associated invariant T (MAIT) cells are rapid responders to infection, but their role and characteristics in the early course of sepsis remain unknown. Here, we evaluate the early MAIT cell characteristics in the blood of patients triggering a clinical sepsis alert system at the emergency department.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Peripheral blood mononuclear cells were isolated from freshly drawn blood and immediately stained. MAIT cell phenotyping analyses were conducted using multiparameter flow cytometry. All analyses were completed prior to the stratification of patients into sepsis or non-sepsis groups. Soluble factors in plasma were measured using a multiplex assay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Unsupervised high-dimensional phenotyping identified distinct MAIT cell activation profiles in sepsis and non-sepsis groups. Among sepsis patients, hierarchical clustering of MAIT cell phenotypes separated clinical endotypes into three groups with different infection focus, severity and aetiology. A prominent characteristic of sepsis severity was high expression of CD69 on MAIT cells, which was associated with organ dysfunction, lymphopenia and poor outcome. Plasma levels of IL-12, IL-15, TNF, IFNγ and CXCL10 correlated with the magnitude of MAIT cell activation in sepsis patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These clinical endotype-specific MAIT cell phenotypes presenting already in the emergency department are of interest for early patient identification and prognostication in sepsis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"14 3","pages":""},"PeriodicalIF":4.6,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70028","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}