Clinical & Translational Immunology最新文献

{"title":"Sustained response to rituximab in an ANCA-negative necrotizing vasculitis with initial detection of Corynebacterium kroppenstedtii","authors":"Nadine Al-Azem,&nbsp;Anna Knothe,&nbsp;Jan-Dirk Raguse,&nbsp;Inga Nierkamp,&nbsp;Achim Georg Beule,&nbsp;Claudia Rudack,&nbsp;Friedericke Müller,&nbsp;Anne Kerlikowki,&nbsp;Eva Wardelmann,&nbsp;Hermann Pavenstädt,&nbsp;Martin A Kriegel,&nbsp;Rebecca Hasseli","doi":"10.1002/cti2.70119","DOIUrl":"10.1002/cti2.70119","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>In this case, we present a patient with rapidly progressive unilateral destructive orbital and midface inflammation. Initial detection of <i>Corynebacterium kroppenstedtii</i> was followed by a consistent course of localised necrotizing small-vessel vasculitis, which was responsive to B-cell depletion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A 79-year-old woman presented with acute left periorbital pain, tearing and purulent discharge. The workup included serial microbiological cultures, fungal and mycobacterial testing, molecular diagnostics, CT/MRI/PET-CT imaging, multiple surgical biopsies with histopathology and special stains, ANCA testing, and multidisciplinary treatments (antimicrobials, glucocorticoids, methotrexate and rituximab). The clinical course, laboratory work, imaging studies, histological analysis and response to treatment were thoroughly reviewed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Initial conjunctival culture revealed <i>C</i>. <i>kroppenstedtii</i> and clindamycin and vancomycin was initiated. Despite escalating antimicrobials, the patient developed progressive inflammation with sinus destruction, cutaneous fistula and cheek abscess, requiring orbital exenteration. The biopsies revealed chronic inflammation with multinucleated giant cells, focal necrosis and small-vessel vasculitis. ANCA remained negative, and subsequent testing was negative. High-dose prednisolone improved the patient, prompting the discontinuation of methotrexate because of pancytopenia. Rituximab-induced remission allowed for steroid tapering and rituximab maintenance, which controlled the disease without complications.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This case illustrates a rare, localised ANCA-negative necrotizing small-vessel vasculitis with destructive orbital involvement and initial detection of <i>C. kroppenstedtii</i>. Although the pathogenic significance of this finding remains uncertain, the case highlights the importance of comprehensive microbiological and immunological evaluation in atypical destructive inflammatory disease. Sustained disease control was achieved with immunosuppressive therapy including rituximab after persistent infection had been excluded.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 8","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13458720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148710772","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":"Humoral and cellular responses to SARS-CoV-2 variants after ancestral COVID-19 vaccines in people with HIV and lung transplant recipients","authors":"David WJ Griffin,&nbsp;Paul A Gill,&nbsp;Irene Boo,&nbsp;Shir Sun,&nbsp;Raffi Gugasyan,&nbsp;Alina Wang,&nbsp;Scott J Bornheimer,&nbsp;Stuart Turville,&nbsp;Anupriya Aggarwal,&nbsp;Greg I Snell,&nbsp;Glen P Westall,&nbsp;Emily SJ Edwards,&nbsp;Anna Coldham,&nbsp;Menno C van Zelm,&nbsp;Heidi E Drummer,&nbsp;James H McMahon","doi":"10.1002/cti2.70117","DOIUrl":"10.1002/cti2.70117","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Immunocompromised hosts have reduced immune responses to COVID-19 vaccination, and more severe disease. Antibody responses correlate with protection but markers of immunity vary across a spectrum of immunocompromise. We compared serologic and cellular responses following Ancestral COVID-19 vaccines in healthy controls (HC), people with HIV (PWH) and lung transplant (LTx) recipients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Anti-spike receptor binding domain (RBD) IgG, neutralising antibodies (nAb) and T-cell responses were assessed one-month post-dose 2 and dose 3 of Ancestral COVID-19 vaccination in HC, PWH and LTx. NAb responses to Ancestral, Delta and Omicron BA.2 and BA.5 variants were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Twenty-nine HC, 21 PWH and 12 LTx recipients were included. PWH demonstrated lower anti-RBD-IgG responses (median post-dose 3: 80.3 μg mL⁻¹ vs 43.3 μg mL⁻¹, <i>P</i> = 0.03) to mRNA COVID-19 vaccination than HC, while LTx recipients displayed diminished responses following any vaccine (15.3 μg mL⁻¹ vs 74.0 μg mL⁻¹, <i>P</i> = 0.01). Dose 3 increased anti-RBD-IgG concentrations and nAb responses in HC and PWH, though Omicron variant neutralisation was attenuated. LTx recipients mounted limited nAb responses. PWH and HC had no difference in nAb responses for Ancestral (median 1738 vs 486.2, <i>P</i> &gt; 0.99) or BA.5 variants (median 34.0 vs 67.9, <i>P</i> &gt; 0.99). Compared with HC, PWH and LTx demonstrated reduced frequencies of SARS-CoV-2-specific memory T cells and a reduced functional memory T-cell response in LTx.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Although Dose 3 was beneficial, LTx recipients demonstrated lower serological responses than HC, while reductions were modest in PWH. Immunocompromised groups had reduced but detectable SARS-CoV-2-specific T-cell responses, demonstrating the utility of COVID-19 vaccination despite poorer serological responses.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 8","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13433146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148672713","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":"CD4+ T-cell responses directed towards A/H5N1-derived haemagglutinin peptides increase in patients with seasonal influenza A virus infection","authors":"Lilith F Allen,&nbsp;Louise C Rowntree,&nbsp;Mitchell Jenzen,&nbsp;Ruth R Hagen,&nbsp;Nathan P Croft,&nbsp;Fiona James,&nbsp;Genevieve E Martin,&nbsp;Anthony W Purcell,&nbsp;Patricia T Illing,&nbsp;Steven Y C Tong,&nbsp;Allen C Cheng,&nbsp;Tom C Kotsimbos,&nbsp;Jason A Trubiano,&nbsp;Katherine Kedzierska,&nbsp;Thi H O Nguyen","doi":"10.1002/cti2.70118","DOIUrl":"https://doi.org/10.1002/cti2.70118","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Recent outbreak of influenza A/H5N1 viral infections in birds and mammals worldwide prompted renewed concerns over an emerging H5N1-related influenza pandemic in the generally immunologically-naive global population. Cross-reactive CD4⁺ T cells between A/H1N1 and A/H5N1 subtypes targeting internal and surface influenza proteins have been identified in humans, indicating some protection against severe and fatal A/H5N1 infection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To detect T-cell responses towards H1 and H5 viruses, we stimulated PBMCs from patients hospitalised with seasonal influenza A viruses, alongside healthy individuals, with overlapping peptide pools spanning hemagglutinin (HA) and neuraminidase (NA) of A/Vietnam/1203/2004 (H5N1) and A/New York/18/2009 (H1N1-pdm09-like) viruses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Majority of acutely infected and healthy participants (100% and 75%, respectively) had detectable CD4⁺ and CD8⁺ T-cell responses towards H1-HA and H5-HA, whereas 30–80% of individuals had detectable H5-NA responses. H1 and H5 HA-specific CD4⁺ T-cell responses highly correlated, suggesting some level of cross-reactivity between T-cell responses directed against H1 and H5 subtypes. HA-specific CD4⁺ T-cell responses were increased in influenza patients compared to healthy participants. We found no differences in H1- and H5-specific T cell responses between those born pre- and post-1968, irrespective of infection status. Sequence alignment of H1 and H5 viruses identified high conservation in the HA2 stalk subunit (81.53%). CD4⁺ T-cell immunity towards immunodominant HA_306–318 epitope, restricted by several HLA-DRB1 molecules, revealed limited cross-reactivity between Group 1 and Group 2 HA-subtypes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>We define correlative H1- and H5-specific CD4⁺ T-cell responses during seasonal influenza A virus infection, likely reflecting some level of H1/H5 T cell cross-reactivity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 8","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70118","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148652461","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 IL-10 levels during CRS are negatively associated with NK-cell recovery after CAR-T cell therapy","authors":"Xindi Wang,&nbsp;Wenjing Luo,&nbsp;Yingying Li,&nbsp;Jianghua Wu,&nbsp;Lu Tang,&nbsp;Chenggong Li,&nbsp;Qiaolin Liu,&nbsp;Zhihan Chen,&nbsp;Yu Hu,&nbsp;Heng Mei","doi":"10.1002/cti2.70116","DOIUrl":"10.1002/cti2.70116","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Immune reconstitution following chimeric antigen receptor (CAR)-T cell therapy remains a critical clinical challenge, and the determinants of natural killer (NK)-cell recovery are not fully understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We longitudinally monitored natural killer (NK)-cell recovery in 64 patients during the first year after CD19-directed CAR-T cell therapy, analysing NK-cell counts and surface receptor expression. Associations between cytokine release syndrome (CRS), cytokine profiles, and NK-cell numerical reconstitution were evaluated, and mechanistic insights were explored using <i>in vitro</i> NK-cell assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>NK-cell numerical and phenotypic recovery was impaired within the first month after CAR-T cell infusion. Notably, NK-cell numerical recovery was significantly delayed in patients who developed CRS. A reduced NK-to-T cell ratio at one-month post-infusion was associated with a markedly increased risk of viral infection (hazard ratio = 4.512). Elevated interleukin (IL)-10 levels during CRS were inversely associated with NK-cell recovery. Patients with high IL-10 levels exhibited delayed NK-cell reconstitution, which was independently validated in two external cohorts. Mechanistically, <i>in vitro</i> exposure of NK cells to IL-10 promoted caspase-3 activation, increased apoptosis, and enhanced reactive oxygen species accumulation and lipid peroxidation. Rescue experiments using ferrostatin-1 and Z-VAD-FMK further supported the involvement of IL-10 in apoptosis and ferroptosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings highlight a previously underappreciated role of IL-10 in shaping NK-cell reconstitution post-CAR-T cell therapy, particularly in the setting of CRS. Patients with CRS accompanied by elevated IL-10 levels may benefit from anti-inflammatory interventions or therapeutic strategies aimed at promoting NK-cell recovery.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13396887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148583234","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":"Safety and immunogenicity of an adjuvanted human onchocerciasis vaccine candidate, OvMANE1: preclinical evaluation in a mice model","authors":"Derrick Neba Nebangwa,&nbsp;Mary Teke Efeti,&nbsp;Sonia M. E. Momnougui,&nbsp;Cabirou Mounchili Shintouo,&nbsp;Robert Adamu Shey,&nbsp;Rene Bilingwe Ayiseh,&nbsp;Fidele Ntie-Kang,&nbsp;Stephen Mbigha Ghogomu","doi":"10.1002/cti2.70114","DOIUrl":"10.1002/cti2.70114","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Onchocerciasis, caused by the filarial worm <i>Onchocerca volvulus</i>, remains a major public health challenge because of the limitations of ivermectin-based control strategies, thereby highlighting the need for more innovative tools such as vaccines.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>This study investigated the safety and immunogenicity of a novel multi-epitope chimeric antigen, <i>Ov</i>MANE1 formulated with Freund's adjuvant, in BALB/c mice. Mice were immunised at three time points of 2-week intervals, with blood collected at each point to measure antibody levels and immune cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Adjuvanted-<i>Ov</i>MANE1 exhibited a promising safety profile, revealing neither any physical signs of toxicity nor behavioural abnormalities. Immunological assays showed significant increases in total IgG absorbance (OD 450 nm) after the first (<i>P</i> = 0.0260) and final booster doses (<i>P</i> = 0.026). Total IgG (<i>P</i> = 0.0086) and IgG1 (<i>P</i> = 0.0465) absorbances also increased significantly over the study period, suggesting sustained humoral immunity. Moreover, cellular responses were significantly enhanced, with elevated leucocyte count (<i>P</i> = 0.0190) and increased lymphocyte activity (<i>P</i> = 0.0397) observed in the adjuvanted-<i>Ov</i>MANE1 group compared to the control. Indeed, total leucocytes increased progressively from Day 0 to Day 39, with significant differences recorded in the test group between doses: Days 0–14 (<i>P</i> = 0.0043) and Days 14–28 (<i>P</i> = 0.0079). The pronounced production of relevant antibodies and induction of cellular immunity is indicative of a mixed Th1/Th2 response and antibody-dependent cellular cytotoxicity (ADCC) targeting <i>O. volvulus</i> L3 and/or other larval stages of the parasite.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These results position <i>Ov</i>MANE1 as a promising vaccine candidate against human onchocerciasis. However, further <i>in vivo</i> studies are needed to confirm and expand these findings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13317562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148358653","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":"Early brain-penetrant immunotherapy reverses interferon signature and improves motor outcome in a case of ADAR1-related Aicardi-Goutières syndrome","authors":"Russell C Dale,&nbsp;Jessica Hayes,&nbsp;Velda X Han,&nbsp;Ruwani Dissanayake,&nbsp;Xianzhong Lau,&nbsp;Michelle Farrar,&nbsp;Brian Gloss,&nbsp;Markus Hofer,&nbsp;Esther Tantsis,&nbsp;Michelle Lorentzos,&nbsp;Safiyyah Abbas,&nbsp;Yanick J Crow,&nbsp;Shekeeb Mohammad,&nbsp;Shrujna Patel","doi":"10.1002/cti2.70113","DOIUrl":"https://doi.org/10.1002/cti2.70113","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Aicardi-Goutières syndrome (AGS) is a genetic interferonopathy resulting from defects in nucleic acid metabolism and subsequent enhanced type I interferon signalling. We report how an expedited genomic diagnosis in conjunction with natural history data can enable a long-term brain-penetrant anti-inflammatory regimen to optimise neurodevelopmental outcomes in genetic autoinflammatory brain disorders.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Expedited genomic testing identified compound heterozygous <i>ADAR1</i> mutations. Published natural history data from 33 patients with biallelic <i>ADAR1</i> mutations reported severe disability (GMFCS V) or death in 79%. To reduce neuroinflammation, we commenced a long-term pulsed oral dexamethasone protocol (20 mg/m² for 3 days every 3 weeks) from the age of 11 months, plus ruxolitinib, a Janus Kinase (JAK) inhibitor (5 mg per day).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>At the age of 24 months, the patient was crawling and walking a few steps unaided, with a GMFCS level of II. Single-cell RNA sequencing of 41 164 leukocytes, taken before and after 3 months of treatment and compared to three age matched male controls, showed a reversal of upregulated pan-cellular interferon pathways, with most differentially expressed genes observed in monocytes. On treatment, there was statistically significant downregulation of key autoinflammatory genes, including nucleic acid sensing (<i>CGAS, IFIH1, SAMHD1</i>), interferon-stimulated genes (<i>ISG15 and IFIF44L</i>) and signalling (<i>JAK1</i>). Given the dual immune therapy, it was not possible to define whether the biological effect was related to dexamethasone or JAK inhibitor, or both.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Compared with natural history data, our data suggest that early diagnosis, and the use of early brain-penetrant immune suppressants (dexamethasone), may improve outcomes in <i>ADAR1</i> AGS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 7","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70113","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148343318","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":"Effect of CXCR5, PD-1 and ICOS on B-cell responses and relevance to myasthenia gravis","authors":"Merve Çebi,&nbsp;Arman Çakar,&nbsp;Hacer Durmuş,&nbsp;Yeşim Parman,&nbsp;Güher Saruhan-Direskeneli","doi":"10.1002/cti2.70112","DOIUrl":"10.1002/cti2.70112","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>T follicular helper (Tfh) cells regulate B-cell responses within germinal centres primarily via programmed cell death protein 1 (PD-1) and inducible T-cell costimulator (ICOS), whereas CXC chemokine receptor type 5 (CXCR5)-negative T peripheral helper (Tph) cells provide similar support extra-follicularly. Both subsets contribute to the pathogenesis of acetylcholine receptor-antibody-positive myasthenia gravis (AChR-MG). This study investigated the roles of PD-1, ICOS and CXCR5 in T-cell-mediated B-cell activation to identify therapeutic targets for MG.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>CD4 T cells from 10 healthy controls and six untreated AChR-MG patients were sorted by CXCR5, PD-1 and ICOS expression, stimulated with anti-CD3/CD28, and co-cultured with autologous CD19 B cells. Plasmablast differentiation, total AChR-IgG and cytokine productions were measured.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In healthy donors, PD-1⁺ or ICOS⁺ Tph cells modestly enhanced plasmablasts and IgG production, while CXCR5⁺ Tfh cells co-expressing PD-1 or ICOS induced significantly stronger B-cell responses. In AChR-MG patients, PD-1 expressing T cells promoted plasmablasts, antibody production and cytokine secretion regardless of CXCR5, with amplified effects in CXCR5⁺ co-cultures.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>PD-1 expression on CD4⁺ T cells is associated with increased B-cell helper capacity. This effect is more pronounced in Tfh-related contexts and is linked to dysregulated humoral immune responses in MG. PD-1 appears to play a central role in the pathogenesis of MG, primarily through Tfh cell activity.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13283754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148300297","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":"Development and functional adaptation of intestinal macrophages across the lifespan","authors":"Baha Mustafa,&nbsp;Elisa L Hill-Yardin,&nbsp;Sarah J Spencer","doi":"10.1002/cti2.70111","DOIUrl":"10.1002/cti2.70111","url":null,"abstract":"<p>Macrophages of the gastrointestinal system are central regulators of gut development, homeostasis and disease, yet their origin, functional diversification and life stage-specific roles remain incompletely integrated. This review aimed to provide a comprehensive synthesis of current knowledge on intestinal macrophage ontogeny, heterogeneity and function from prenatal development through adulthood and into the aging phase. We highlight emerging evidence defining embryonic and monocyte-derived macrophage populations, their specialised roles in tissue remodelling, immune regulation, vascular and neural support, and their dynamic turnover across the lifespan. The review also examines how disruption of key regulatory pathways, including those relating to interleukin 10 (IL10), transforming growth factor (TGFβ) and metabolic signalling, contributes to macrophage dysfunction in inflammatory bowel disease, as an example of a gastrointestinal disorder with macrophage involvement. By integrating findings from lineage-tracing, single-cell transcriptomics and functional studies, this review provides a unified framework for understanding intestinal macrophage biology across life stages. This review provides a strengthened understanding of intestinal macrophage biology and establishes a knowledge base for translational therapies that can modify macrophage function to target inflammatory disorders and maintain gut health.</p>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 6","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13270256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148269567","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":"Single-cell and repertoire profiling reveals immune remodelling in paediatric upper airway: insights from adenoid hypertrophy","authors":"Chao Wang,&nbsp;Yufei Pan,&nbsp;Xiao Han,&nbsp;Kai Sun,&nbsp;Jing Li,&nbsp;Yuanyuan Lu,&nbsp;Zhenkun Yu","doi":"10.1002/cti2.70101","DOIUrl":"https://doi.org/10.1002/cti2.70101","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>To characterise the immune cellular landscape and paired B-cell and T-cell receptor repertoires of hypertrophic adenoids in children with obstructive sleep apnoea.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We performed 10x Genomics 5′ single-cell RNA sequencing with paired V(D)J profiling on adenoid tissues from children (AH, <i>n</i> = 4; control, <i>n</i> = 4) and analysed 72 076 high-quality cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared with controls, AH adenoids exhibited an expanded B-cell compartment (62.26% vs 51.94%, <i>P</i> = 0.029) and a modest increase in plasmacytoid dendritic cells (0.37% vs 0.15%, <i>P</i> = 0.029), accompanied by reduced T-cell representation (34.19% vs 44.54%, <i>P</i> = 0.029). Within the B-cell compartment, GC B cell populations were expanded in AH, particularly Cycling B cells (15.07% vs 2.86%, <i>P</i> = 0.029), whereas memory B cells were reduced (21.48% vs 32.18%, <i>P</i> = 0.029). B-cell receptor analysis demonstrated reduced somatic hypermutation frequencies across multiple mature B-cell subsets in AH, accompanied by an isotype distribution skewed towards IgM with reduced class-switched fractions. Although CD8⁺ tissue-resident memory T-cell (TRM) frequencies were similar between groups, CD8⁺ TRM in AH adenoids displayed interferon-polarised and antigen-processing signatures, and T-cell clonal expansion occurred predominantly within this subset.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>These findings suggest that AH is not merely an anatomic cause of upper airway obstruction but also an immunologically active mucosal state associated with ongoing immune remodelling and antiviral defence.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 6","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70101","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148174302","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":"Control of poorly immunogenic tumors with systemic STING agonist-loaded liposomes targeting cross-presenting dendritic cells","authors":"Bijun Zeng,&nbsp;Meghna Talekar,&nbsp;Thais Aragao-Horoiwa,&nbsp;Amy Cameron,&nbsp;Guangzu Zhao,&nbsp;Yulia Zybina,&nbsp;Wendy Blumenschein,&nbsp;Karyn van de Mark,&nbsp;Wittaya Suwakulsiri,&nbsp;Gretchen A Baltus,&nbsp;Riccardo Dolcetti,&nbsp;Ranjeny Thomas","doi":"10.1002/cti2.70110","DOIUrl":"https://doi.org/10.1002/cti2.70110","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Cancer vaccines combine tumor antigen and adjuvant to drive an anti-tumor immune response. Clec9A-targeted nanoparticles directing CD4 and CD8 neo-epitopes to cross-presenting dendritic cells (DCs) stimulate adjuvant-free therapeutically effective tumor-specific immunity. However, personalised neo-epitopes limit the scalability of Clec9A nanoparticles for clinical translation. Since Clec9A⁺ DCs constitutively present relevant neoepitopes in tumors but are suppressed in tumor microenvironments, we developed Clec9A-targeted STING or RIG-I liposomes to enhance endogenous tumor immunity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Liposomes encapsulating RIG-I or the STING agonist MSA-1 and functionalised with Clec9A binding peptide WH were optimised for uptake by Clec9A⁺ conventional and plasmacytoid DCs <i>in vivo</i>. Biodistribution after i.v. administration was determined with <i>in vivo</i> imaging and cellular uptake and activation with flow cytometry. Plasma was analysed for type 1 interferon (IFN) by ELISA and liver, spleen, tumor, blood, kidney, heart and tumor draining lymph node transcriptomes were analysed with Nanostring. Effects on tumor growth and survival, and tumor-specific T cells were evaluated using the B16 melanoma model.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Clec9A-targeting liposomes administered i.v. were distributed to spleen, liver and tumor and were taken up by cross-presenting and plasmacytoid DCs. Type 1 IFN production and DC, B- and T-cell activation were more effective with i.v. Clec9A-STING than Clec9A-RIG-I liposomes. Intravenous Clec9A-STING liposomes stimulated IFN-dependent transcription in blood, lung, tumor, and draining lymph nodes. Intravenous Clec9A-STING liposomes, or intra-tumoral Clec9A-RIG-I liposomes significantly suppressed B16-F10 melanoma growth and induced neo-epitope and survivin-specific CD4⁺ and CD8⁺ T-cell responses.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Clec9A-STING liposomes are a scalable, translatable tumor-targeted immunotherapy platform.</p>\u0000 </section>\u0000 </div>","PeriodicalId":152,"journal":{"name":"Clinical & Translational Immunology","volume":"15 6","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cti2.70110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148173681","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}