Clinical & Translational Immunology最新文献

{"title":"SARS-CoV-2-infected human airway epithelial cell cultures uniquely lack interferon and immediate early gene responses caused by other coronaviruses","authors":"Ying Wang,&nbsp;Melissa Thaler,&nbsp;Clarisse Salgado-Benvindo,&nbsp;Nathan Ly,&nbsp;Anouk A Leijs,&nbsp;Dennis K Ninaber,&nbsp;Philip M Hansbro,&nbsp;Fia Boedijono,&nbsp;Martijn J van Hemert,&nbsp;Pieter S Hiemstra,&nbsp;Anne M van der Does,&nbsp;Alen Faiz","doi":"10.1002/cti2.1503","DOIUrl":"https://doi.org/10.1002/cti2.1503","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of a class of highly pathogenic coronaviruses. The large family of coronaviruses, however, also includes members that cause only mild symptoms, like human coronavirus-229E (HCoV-229E) or OC43 (HCoV-OC43). Unravelling how molecular (and cellular) pathophysiology differs between highly and low pathogenic coronaviruses is important for the development of therapeutic strategies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Here, we analysed the transcriptome of primary human bronchial epithelial cells (PBEC), differentiated at the air–liquid interface (ALI) after infection with SARS-CoV-2, SARS-CoV, Middle East Respiratory Syndrome (MERS)-CoV and HCoV-229E using bulk RNA sequencing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>ALI-PBEC were efficiently infected by all viruses, and SARS-CoV, MERS-CoV and HCoV-229E infection resulted in a largely similar transcriptional response. The response to SARS-CoV-2 infection differed markedly as it uniquely lacked the increase in expression of immediate early genes, including <i>FOS</i>, <i>FOSB</i> and <i>NR4A1</i> that was observed with all other coronaviruses. This finding was further confirmed in publicly available experimental and clinical datasets. Interfering with NR4A1 signalling in Calu-3 lung epithelial cells resulted in a 100-fold reduction in extracellular RNA copies of SARS-CoV-2 and MERS-CoV, suggesting an involvement in virus replication. Furthermore, a lack in induction of interferon-related gene expression characterised the main difference between the highly pathogenic coronaviruses and low pathogenic viruses HCoV-229E and HCoV-OC43.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our results demonstrate a previously unknown suppression of a host response gene set by SARS-CoV-2 and confirm a difference in interferon-related gene expression between highly pathogenic and low pathogenic coronaviruses.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1503","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140553106","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":"Chimeric antigen receptor T cells in the fast lane among autoimmune disease therapies","authors":"Zhoujie Ding,&nbsp;David Tarlinton","doi":"10.1002/cti2.1502","DOIUrl":"https://doi.org/10.1002/cti2.1502","url":null,"abstract":"<p>In this commentary, we highlight recent studies demonstrating the feasibility and promise of chimeric antigen receptor (CAR) T-cell therapy in treating a number of autoimmune disorders including systemic lupus erythematosus and compare CAR T cells to other therapies aimed at depleting B-lineage cells in treating such diseases.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1502","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140546872","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":"CD177 drives the transendothelial migration of Treg cells enriched in human colorectal cancer","authors":"Shouyu Ke,&nbsp;Yi Lei,&nbsp;Yixian Guo,&nbsp;Feng Xie,&nbsp;Yimeng Yu,&nbsp;Haigang Geng,&nbsp;Yiqing Zhong,&nbsp;Danhua Xu,&nbsp;Xu Liu,&nbsp;Fengrong Yu,&nbsp;Xiang Xia,&nbsp;Zizhen Zhang,&nbsp;Chunchao Zhu,&nbsp;Wei Ling,&nbsp;Bin Li,&nbsp;Wenyi Zhao","doi":"10.1002/cti2.1506","DOIUrl":"https://doi.org/10.1002/cti2.1506","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Regulatory T (Treg) cells regulate immunity in autoimmune diseases and cancers. However, immunotherapies that target tumor-infiltrating Treg cells often induce unwanted immune responses and tissue inflammation. Our research focussed on exploring the expression pattern of CD177 in tumor-infiltrating Treg cells with the aim of identifying a potential target that can enhance immunotherapy effectiveness.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Single-cell RNA sequencing (scRNA-seq) data and survival data were obtained from public databases. Twenty-one colorectal cancer patient samples, including fresh tumor tissues, peritumoral tissues and peripheral blood mononuclear cells (PBMCs), were analysed using flow cytometry. The transendothelial activity of CD177⁺ Treg cells was substantiated using <i>in vitro</i> experiments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>ScRNA-seq and flow cytometry results indicated that CD177 was exclusively expressed in intratumoral Treg cells. CD177⁺ Treg cells exhibited greater activation status and expressed elevated Treg cell canonical markers and immune checkpoint molecules than CD177⁻ Treg cells. We further discovered that both intratumoral CD177⁺ Treg cells and CD177-overexpressing induced Treg (iTreg) cells had lower levels of PD-1 than their CD177⁻ counterparts. Moreover, CD177 overexpression significantly enhanced the transendothelial migration of Treg cells <i>in vitro</i>.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These results demonstrated that Treg cells with higher CD177 levels exhibited an enhanced activation status and transendothelial migration capacity. Our findings suggest that CD177 may serve as an immunotherapeutic target and that overexpression of CD177 may improve the efficacy of chimeric antigen receptor T (CAR-T) cell therapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1506","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140541096","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":"Identification of distinct immune signatures in inclusion body myositis by peripheral blood immunophenotyping using machine learning models","authors":"Emily McLeish,&nbsp;Anuradha Sooda,&nbsp;Nataliya Slater,&nbsp;Kelly Beer,&nbsp;Ian Cooper,&nbsp;Frank L Mastaglia,&nbsp;Merrilee Needham,&nbsp;Jerome D Coudert","doi":"10.1002/cti2.1504","DOIUrl":"https://doi.org/10.1002/cti2.1504","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Inclusion body myositis (IBM) is a progressive late-onset muscle disease characterised by preferential weakness of quadriceps femoris and finger flexors, with elusive causes involving immune, degenerative, genetic and age-related factors. Overlapping with normal muscle ageing makes diagnosis and prognosis problematic.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We characterised peripheral blood leucocytes in 81 IBM patients and 45 healthy controls using flow cytometry. Using a random forest classifier, we identified immune changes in IBM compared to HC. K-means clustering and the random forest one-versus-rest model classified patients into three immunophenotypic clusters. Functional outcome measures including mTUG, 2MWT, IBM-FRS, EAT-10, knee extension and grip strength were assessed across clusters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The random forest model achieved a 94% AUC ROC with 82.76% specificity and 100% sensitivity. Significant differences were found in IBM patients, including increased CD8⁺ T-bet⁺ cells, CD4⁺ T cells skewed towards a Th1 phenotype and altered γδ T cell repertoire with a reduced proportion of Vγ9⁺Vδ2⁺ cells. IBM patients formed three clusters: (i) activated and inflammatory CD8⁺ and CD4⁺ T-cell profile and the highest proportion of anti-cN1A-positive patients in cluster 1; (ii) limited inflammation in cluster 2; (iii) highly differentiated, pro-inflammatory T-cell profile in cluster 3. Additionally, no significant differences in patients' age and gender were detected between immunophenotype clusters; however, worsening trends were detected with several functional outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings unveil distinct immune profiles in IBM, shedding light on underlying pathological mechanisms for potential immunoregulatory therapeutic development.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 4","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1504","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140345595","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":"Synergistic integration of histone deacetylase inhibitors apparently enhances the cytokine-induced killer cell efficiency in multiple myeloma via the NKG2D pathway","authors":"Jingjing Pu,&nbsp;Amit Sharma,&nbsp;Ting Liu,&nbsp;Jian Hou,&nbsp;Ingo GH Schmidt-Wolf","doi":"10.1002/cti2.1500","DOIUrl":"https://doi.org/10.1002/cti2.1500","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The rapid recognition of epigenetic manipulation's potential in restricting cancer cell capabilities spurred translational initiatives, including histone deacetylase inhibitors (HDACis). Clinical trials on multiple myeloma (MM) demonstrated substantial benefits of HDACis, coupled with promising outcomes from cytokine-induced killer cell (CIK) immunotherapy. Intriguingly, the unexplored synergy of HDACis and CIK cell immunotherapy in MM prompted our study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We examined clinically relevant HDACis (panobinostat/LBH589 and romidepsin) alongside CIK cells derived from peripheral blood mononuclear cells across diverse MM cell lines (U266, RPMI8226, OPM-2 and NCI-H929). Utilising various <i>in vitro</i> methodologies, we investigated how HDACis enhance CIK cell lysis of myeloma cells through NKG2D/NKG2D ligand interactions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The results of our analysis indicated several key findings. (1) Enhanced cytotoxicity of CIK cells in MM cells when combined with HDACis. (2) Significant increase in apoptosis, suggesting HDACis and CIK may together enhance apoptotic effects in specific MM cell lines. (3) Elevated IFN-γ secretion and alterations in granzyme B secretion because of the independent activity of HDACis. (4) Notably, HDACis increased the expression of MICA/B and ULBP2, crucial for inducing antitumor cytotoxicity of NKT cells. Validation through NKG2D receptor blocking in CIK cells with a purified mouse antihuman NKG2D antibody further supported our findings.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our analyses provide sufficient evidence to consider this clinically forgotten instance (HDACis-CIK cell combination) as a therapeutic priority for MM treatment. Furthermore, we suggest that NKG2D/NKG2D-ligand interactions activating NK/NKT cells may contribute to enhanced myeloma cell lysis in response to HDACis treatment by CIK cells.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 3","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1500","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140209573","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":"Exploring NK cell receptor dynamics in paediatric leukaemias: implications for immunotherapy and prognosis","authors":"Cui Tu,&nbsp;Irina Buckle,&nbsp;Ingrid Leal Rojas,&nbsp;Gustavo Rodrigues Rossi,&nbsp;David P Sester,&nbsp;Andrew S Moore,&nbsp;Kristen Radford,&nbsp;Camille Guillerey,&nbsp;Fernando Souza-Fonseca-Guimaraes","doi":"10.1002/cti2.1501","DOIUrl":"https://doi.org/10.1002/cti2.1501","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Immunotherapies targeting natural killer (NK) cell receptors have shown promise against leukaemia. Unfortunately, cancer immunosuppressive mechanisms that alter NK cell phenotype prevent such approaches from being successful. The study utilises advanced cytometry to examine how cancer immunosuppressive pathways affect NK cell phenotypic changes in clinical samples.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this study, we conducted a high-dimensional examination of the cell surface expression of 16 NK cell receptors in paediatric patients with acute myeloid leukaemia and acute lymphoblastic leukaemia, as well as in samples of non-age matched adult peripheral blood (APB) and umbilical cord blood (UCB). An unsupervised analysis was carried out in order to identify NK cell populations present in paediatric leukaemias.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>We observed that leukaemia NK cells clustered together with UCB NK cells and expressed relatively higher levels of the NKG2A receptor compared to APB NK cells. In addition, CD56^dimCD16⁺CD57⁻ NK cells lacking NKG2A expression were mainly absent in paediatric leukaemia patients. However, CD56^br NK cell populations expressing high levels of NKG2A were highly represented in paediatric leukaemia patients. NKG2A expression on leukaemia NK cells was found to be positively correlated with the expression of its ligand, suggesting that the NKG2A-HLA-E interaction may play a role in modifying NK cell responses to leukaemia cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We provide an in-depth analysis of NK cell populations in paediatric leukaemia patients. These results support the development of immunotherapies targeting immunosuppressive receptors, such as NKG2A, to enhance innate immunity against paediatric leukaemia.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 3","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1501","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140192318","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":"CD39 expression defines exhausted CD4+ T cells associated with poor survival and immune evasion in human gastric cancer","authors":"Zhen-quan Duan,&nbsp;Yu-xian Li,&nbsp;Yuan Qiu,&nbsp;Yang Shen,&nbsp;Ying Wang,&nbsp;Yuan-yuan Zhang,&nbsp;Bao-hang Zhu,&nbsp;Xiao-hong Yu,&nbsp;Xue-ling Tan,&nbsp;Weisan Chen,&nbsp;Yuan Zhuang,&nbsp;Ping Cheng,&nbsp;Wei-jun Zhang,&nbsp;Quan-ming Zou,&nbsp;Dai-yuan Ma,&nbsp;Liu-sheng Peng","doi":"10.1002/cti2.1499","DOIUrl":"https://doi.org/10.1002/cti2.1499","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>CD4⁺ T cell helper and regulatory function in human cancers has been well characterised. However, the definition of tumor-infiltrating CD4⁺ T cell exhaustion and how it contributes to the immune response and disease progression in human gastric cancer (GC) remain largely unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 128 GC patients were enrolled in the study. The expression of CD39 and PD-1 on CD4⁺ T cells in the different samples was analysed by flow cytometry. GC-infiltrating CD4⁺ T cell subpopulations based on CD39 expression were phenotypically and functionally assessed. The role of CD39 in the immune response of GC-infiltrating T cells was investigated by inhibiting CD39 enzymatic activity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In comparison with CD4⁺ T cells from the non-tumor tissues, significantly more GC-infiltrating CD4⁺ T cells expressed CD39. Most GC-infiltrating CD39⁺CD4⁺ T cells exhibited CD45RA⁻CCR7⁻ effector–memory phenotype expressing more exhaustion-associated inhibitory molecules and transcription factors and produced less TNF-α, IFN-γ and cytolytic molecules than their CD39⁻CD4⁺ counterparts. Moreover, <i>ex vivo</i> inhibition of CD39 enzymatic activity enhanced their functional potential reflected by TNF-α and IFN-γ production. Finally, increased percentages of GC-infiltrating CD39⁺CD4⁺ T cells were positively associated with disease progression and patients' poorer overall survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study demonstrates that CD39 expression defines GC-infiltrating CD4⁺ T cell exhaustion and their immunosuppressive function. Targeting CD39 may be a promising therapeutic strategy for treating GC patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 3","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1499","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140145681","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":"Graft-versus-leukaemia immunity is retained following treatment with post-transplant cyclophosphamide alone or combined with tocilizumab in humanised mice","authors":"Chloe Sligar,&nbsp;Ellie Reilly,&nbsp;Peter Cuthbertson,&nbsp;Kara L Vine,&nbsp;Katrina M Bird,&nbsp;Amal Elhage,&nbsp;Stephen I Alexander,&nbsp;Ronald Sluyter,&nbsp;Debbie Watson","doi":"10.1002/cti2.1497","DOIUrl":"https://doi.org/10.1002/cti2.1497","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Donor haematopoietic stem cell transplantation treats leukaemia by inducing graft-versus-leukaemia (GVL) immunity. However, this benefit is often mitigated by graft-versus-host disease (GVHD), which is reduced by post-transplant cyclophosphamide (PTCy) alone or combined with tocilizumab (TOC) in humanised mice. This study established a preclinical humanised mouse model of GVL and investigated whether PTCy alone or combined with TOC impacts GVL immunity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>NOD-<i>scid</i>-IL2Rγ^null mice were injected with 2 × 10⁷ human peripheral blood mononuclear cells (hPBMCs) on day 0 and with 1 × 10⁶ THP-1 acute myeloid leukaemia cells on day 14. In subsequent experiments, mice were also injected with PTCy (33 mg kg⁻¹) or Dulbecco's phosphate buffered saline (PBS) on days 3 and 4, alone or combined with TOC or control antibody (25 mg kg⁻¹) twice weekly for 28 days. Clinical signs of disease were monitored until day 42.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Mice with hPBMCs from three different donors and THP-1 cells showed similar survival, clinical score and weight loss. hCD33⁺ leukaemia cells were minimal in mice reconstituted with hPBMCs from two donors but present in mice with hPBMCs from a third donor, suggesting donor-specific GVL responses. hPBMC-injected mice treated with PTCy alone or combined with TOC (PTCy + TOC) demonstrated prolonged survival compared to control mice. PTCy alone and PTCy + TOC-treated mice with hPBMCs showed minimal hepatic hCD33⁺ leukaemia cells, indicating sustained GVL immunity. Further, the combination of PTCy + TOC reduced histological damage in the lung and liver.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Collectively, this research demonstrates that PTCy alone or combined with TOC impairs GVHD without compromising GVL immunity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 3","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1497","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140135412","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":"Prediction of intravenous immunoglobulin retreatment in children with Kawasaki disease using models combining lymphocyte subset and cytokine profile in an East Asian cohort","authors":"Chun Zhang,&nbsp;Sun Chen,&nbsp;Yan Bian,&nbsp;Xiaohua Qian,&nbsp;Yurui Liu,&nbsp;Liqing Zhao,&nbsp;Jia Shen,&nbsp;Jiani Song,&nbsp;Peng Zhang,&nbsp;Lun Chen,&nbsp;Limin Jiang","doi":"10.1002/cti2.1498","DOIUrl":"https://doi.org/10.1002/cti2.1498","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>For children with Kawasaki disease (KD) at high risk of developing coronary artery lesions and requiring retreatment with intravenous immunoglobulin (IVIG), the availability of accurate prediction models remains limited because of inconsistent variables and unsatisfactory prediction results. We aimed to construct models to predict patient's probability of IVIG retreatment combining children's individual inflammatory characteristics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Clinical manifestations and laboratory examinations of 266 children with KD were retrospectively analysed to build a development cohort data set (DC) and a validation cohort data set (VC). In the DC, binary logistic regression analyses were performed using R language. Nomograms and receiver operating curves were plotted. The concordance index (C index), net reclassification index, integrated discrimination improvement index and confusion matrix were applied to evaluate and validate the models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Models_5V and _9V were established. Both contained variables including the percentages of CD8⁺ T cells, CD4⁺ T cells, CD3⁺ T cells, levels of interleukin (IL)-2R and CRP. Model_9V additionally included variables for IL-6, TNF-α, NT-proBNP and sex, with a C index of 0.86 (95% CI 0.79–0.92). When model_9V was compared with model_5V, the NRI and IDI were 0.15 (95% CI 0.01–0.30, <i>P</i> &lt; 0.01) and 0.07 (95% CI 0.02–0.12, <i>P</i> &lt; 0.01). In the VC, the sensitivity, specificity and precision of model_9V were 1, 0.875 and 0.667, while those of model_5V were 0.833, 0.875 and 0.625.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Model_9V combined cytokine profiles and lymphocyte subsets with clinical characteristics and was superior to model_5V achieving satisfactory predictive power and providing a novel strategy early to identify patients who needed IVIG retreatment.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 3","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1498","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140114287","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":"Unremitting pro-inflammatory T-cell phenotypes, and macrophage activity, following paediatric burn injury","authors":"Donna Langley,&nbsp;Kate Zimmermann,&nbsp;Emma Krenske,&nbsp;Giorgio Stefanutti,&nbsp;Roy M Kimble,&nbsp;Andrew JA Holland,&nbsp;Mark W Fear,&nbsp;Fiona M Wood,&nbsp;Tony Kenna,&nbsp;Leila Cuttle","doi":"10.1002/cti2.1496","DOIUrl":"https://doi.org/10.1002/cti2.1496","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>The aim of this study was to characterise the dynamic immune profile of paediatric burn patients for up to 18 months post-burn.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Flow cytometry was used to measure 25 cell markers, chemokines and cytokines which reflected both pro-inflammatory and anti-inflammatory immune profiles. Peripheral blood mononuclear cells from 6 paediatric burn patients who had returned for repeated burn and scar treatments for &gt; 4 timepoints within 12 months post-burn were compared to four age-matched healthy controls.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>While overall proportions of T cells, NK cells and macrophages remained relatively constant, over time percentages of these immune cells differentiated into effector and proinflammatory cell phenotypes including Th17 and activated γδ T cells. Circulating proportions of γδ T cells increased their expression of pro-inflammatory mediators throughout the burn recovery, with a 3–6 fold increase of IL-17 at 1–3 weeks, and NFκβ 9–18 months post-burn. T-regulatory cell plasticity was also observed, and Treg phenotype proportions changed from systemically reduced skin-homing T-regs (CCR4⁺) and increased inflammatory (CCR6⁺) at 1-month post-burn, to double-positive cell types (CCR4⁺CCR6⁺) elevated in circulation for 18 months post-burn. Furthermore, Tregs were observed to proportionally express less IL-10 but increased TNF-α over 18 months.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Overall, these results indicate the circulating percentages of immune cells do not increase or decrease over time post-burn, instead they become highly specialised, inflammatory and skin-homing. In this patient population, these changes persisted for at least 18 months post-burn, this ‘immune distraction’ may limit the ability of immune cells to prioritise other threats post-burn, such as respiratory infections.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"13 3","pages":""},"PeriodicalIF":5.8,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.1496","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140063852","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}