Journal of immunology最新文献

Pivotal role of voltage-dependent anion channel 2 in pyroptosis induced by spring viremia of carp virus in fish cells. 电压依赖性阴离子通道2在鲤病毒春季病毒血症诱导鱼细胞热亡中的关键作用。

IF 3.4 3区医学

Journal of immunology Pub Date : 2025-10-08 DOI: 10.1093/jimmun/vkaf154

Chen Li, Weiyang Zhao, Yan Gao, Yuanan Lu, Jing Ye, Xueqin Liu

{"title":"Pivotal role of voltage-dependent anion channel 2 in pyroptosis induced by spring viremia of carp virus in fish cells.","authors":"Chen Li, Weiyang Zhao, Yan Gao, Yuanan Lu, Jing Ye, Xueqin Liu","doi":"10.1093/jimmun/vkaf154","DOIUrl":"https://doi.org/10.1093/jimmun/vkaf154","url":null,"abstract":"Spring viremia of carp virus (SVCV) represents a significant threat to cyprinids, particularly common carp (Cyprinus carpio). The disease caused by this virus is characterized by tissue necrosis and petechial hemorrhages. However, the pathogenesis of SVCV infection remains poorly understood. Pyroptosis, a recently identified form of programmed cell death, plays a crucial role in host-pathogen interactions and provides a novel approach for studying inflammation-related diseases. This study demonstrates that SVCV induces gasdermin Eb-dependent pyroptosis through activation of NLRP3 and initiation of cellular inflammatory death. This process results in the production of active caspase-B (p20), mature interleukin-1β, and lactate dehydrogenase release. The gasdermin Eb-dependent pyroptosis induced by SVCV is inhibited by treatment with either an NLRP3 inhibitor or a caspase-B inhibitor. Mechanistic investigations reveal that the SVCV-G protein plays a critical role in inducing pyroptosis, while the host-interacting protein, voltage-dependent anion channel 2 (VDAC2), is essential for inflammasome activation by maintaining NLRP3 protein stability. In vivo experiments show that DIDS, a VDAC2 inhibitor, reduces SVCV-induced pyroptosis and NLRP3 inflammasome activation, thereby alleviating inflammation and tissue damage in zebrafish. Furthermore, zebrafish larvae with VDAC2 gene knockdown exhibit reduced cellular damage from SVCV infection, resulting in increased survival. These findings elucidate a mechanism by which SVCV activates the NLRP3 inflammasome, inducing inflammation and pyroptosis, and provide novel insights into the pathogenesis of SVCV infection.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Non-neutralizing antibodies against SARS-CoV-2 nucleocapsid protein mediate variant transcendent antibody-dependent cellular cytotoxicity. 针对SARS-CoV-2核衣壳蛋白的非中和抗体介导变异超越抗体依赖的细胞毒性。

IF 3.4 3区医学

Journal of immunology Pub Date : 2025-10-08 DOI: 10.1093/jimmun/vkaf123

Anthonia E Osuagwu, Michael Payne, Jürgen Bosch, Uri Mbonye, Kien Nguyen, Jonathan Karn, Anna Bruchez, Christopher L King

{"title":"Non-neutralizing antibodies against SARS-CoV-2 nucleocapsid protein mediate variant transcendent antibody-dependent cellular cytotoxicity.","authors":"Anthonia E Osuagwu, Michael Payne, Jürgen Bosch, Uri Mbonye, Kien Nguyen, Jonathan Karn, Anna Bruchez, Christopher L King","doi":"10.1093/jimmun/vkaf123","DOIUrl":"https://doi.org/10.1093/jimmun/vkaf123","url":null,"abstract":"Vaccination strategies and correlates of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have predominantly focused on the spike (S) protein and neutralizing antibodies. However, the rapid emergence of SARS-CoV-2 variants has reduced the effectiveness of spike-based vaccines and monoclonal antibodies. It remains unclear how non-neutralizing antibodies that target the nucleocapsid (N) protein contribute to protection against SARS-CoV-2 variants, especially their ability to trigger antibody effector functions. These antibodies may function by binding to infected cells and initiating antibody-dependent cellular cytotoxicity (ADCC), eliminating infected cells. In this study, we demonstrate that antibodies from individuals who recovered from coronavirus disease 2019 (COVID-19) infection and/or were vaccinated with the S protein vaccine recognize viral proteins on the surface of infected cells and mediate ADCC-mediated NK cell killing of infected cells. Notably, non-neutralizing antibodies induced in COVID-19 infection recognized non-spike proteins on the surface of SARS-CoV-2 variant-infected cells, and these non-neutralizing antibodies cleared SARS-CoV-2 infected cells following depletion of spike antibodies. We identified N and minimal membrane (M) proteins as the targets of non-neutralizing antibodies on the surface of these variant-infected cells. We show that enriched N-specific antibodies from individuals who recovered from COVID-19 infection more consistently killed SARS-CoV-2 variant-infected cells than antibodies to the spike protein. The observed cross-reactivity and robust ADCC activity mediated by N-specific antibodies across various SARS-CoV-2 variant-infected cells highlight the N protein as an important vaccine target in addition to the S protein. Targeting N may provide more comprehensive and durable immunity against SARS-CoV-2 and its evolving variants.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145251463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Modulation of host lung immunity in Pneumocystis pneumonia: a review of current concepts and future prospects for novel adjunctive immune-based therapies. 肺囊虫肺炎中宿主肺免疫的调节：新辅助免疫治疗的当前概念和未来前景的综述。

IF 3.4 3区医学

Journal of immunology Pub Date : 2025-10-06 DOI: 10.1093/jimmun/vkaf269

Theodore J Kottom, Andrew H Limper

引用次数: 0

Impact of absent in melanoma 2 on head and neck squamous cell carcinoma development. 黑色素瘤2缺失对头颈部鳞状细胞癌发展的影响。

IF 3.4 3区医学

Journal of immunology Pub Date : 2025-10-03 DOI: 10.1093/jimmun/vkaf224

Dakota M Reinartz, Vicente Escamilla-Rivera, Manlin Shao, Stephanie L Tribble, Carlos Caulin, Justin E Wilson

{"title":"Impact of absent in melanoma 2 on head and neck squamous cell carcinoma development.","authors":"Dakota M Reinartz, Vicente Escamilla-Rivera, Manlin Shao, Stephanie L Tribble, Carlos Caulin, Justin E Wilson","doi":"10.1093/jimmun/vkaf224","DOIUrl":"https://doi.org/10.1093/jimmun/vkaf224","url":null,"abstract":"Head and neck squamous cell carcinoma (HNSCC) constitutes 90% of head and neck cancers. HNSCC development is linked to chronic inflammation, while established HNSCC tumors are often immune suppressive. However, both occur through mechanisms that are not fully understood. The cytosolic double-stranded DNA sensor absent in melanoma 2 (AIM2) is an inflammasome-forming protein that also has inflammasome-distinct roles in restricting tumorigenesis by limited PI3K signaling. Here, we used an experimental mouse model of HNSCC, involving treatment of wild-type (WT) and Aim2-/- mice with the carcinogen 4NQO in drinking water. Compared with WT mice, 4NQO-treated Aim2-/- mice exhibited larger tumors and increased tissue dysplasia. 4NQO-treated WT and Aim2-/- mice displayed similar tongue Il6, Tnf, Il1b, Il12, and Il10 expression and no consistent differences in PI3K or inflammasome activation, suggesting AIM2 may not regulate these factors during HNSCC. Instead, Ifng and Irf1 was elevated in 4NQO-treated Aim2-/- mice, suggesting that AIM2 restricts IFN-γ. In line with this, RNA sequencing of total tongue RNA from 4NQO-treated mice revealed that Aim2-/- mice had enhanced expression of genes related to the major histocompatibility complex protein complex, cell killing, and T cell activation compared with WT mice. We also observed increased macrophage infiltration into the tongue epithelium of 4NQO-treated Aim2-/- mice and an increased M1:M2 macrophage ratio. Using Aim2-/-/Rag1-/- double-deficient animals, we found that the adaptive immune compartment was necessary for the enhanced tumorigenesis during AIM2 deficiency. These findings suggest that AIM2 limits the progression of oral tumor development partially through regulating IFN-γ and adaptive immune responses.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Diabetes and insulin resistance alters ligamentum flavum-derived fibroblast responses in an AKT2-dependent manner. 糖尿病和胰岛素抵抗以akt2依赖的方式改变黄韧带衍生成纤维细胞的反应。

IF 3.4 3区医学

Journal of immunology Pub Date : 2025-10-03 DOI: 10.1093/jimmun/vkaf233

Eleni Paflioti, Evangelia Kandylaki, Ioannis Sperelakis, Georgios Kontakis, Christos Tsatsanis

{"title":"Diabetes and insulin resistance alters ligamentum flavum-derived fibroblast responses in an AKT2-dependent manner.","authors":"Eleni Paflioti, Evangelia Kandylaki, Ioannis Sperelakis, Georgios Kontakis, Christos Tsatsanis","doi":"10.1093/jimmun/vkaf233","DOIUrl":"https://doi.org/10.1093/jimmun/vkaf233","url":null,"abstract":"Fibroblasts participate in inflammatory responses and play a critical role in the switch from acute to persistent inflammation. Whether fibroblast responses are modulated by signals from their microenvironment is not well established. Insulin signaling and insulin resistance modulate responsiveness of innate immune cells to inflammatory signals. Herein, we investigated whether fibroblast responsiveness is affected by the tissue microenvironment. As a source of fibroblasts, we used ligamentum flavum-derived fibroblasts, being a tissue that is inflamed in the context of ligamentum flavum hypertrophy. The results showed that fibroblasts from patients with ligamentum flavum hypertrophy were hyporesponsive to TLR2 signals. Since ligamentum flavum hypertrophy is associated with obesity, we utilized ligamentum flavum-derived fibroblasts from obese and lean mice. Fibroblasts from insulin-resistant obese mice expressed increased Collagen1a1 and produced more IL-6 in response to TLR2 and TLR4 signals. Insulin signaling was altered in ligamentum flavum-derived fibroblasts from obese mice, resulting in reduced insulin-induced AKT1 phosphorylation and increased insulin-induced AKT2 phosphorylation. Ligamentum flavum-derived fibroblasts from AKT2-deficient mice were hyporesponsive to TLR signals, in contrast to these from obese mice, suggesting that active AKT2 signaling is required to support responsiveness of fibroblasts. Basal respiration and stress-induced glycolysis were elevated in fibroblasts from AKT2-/- and obese mice, suggesting that even though their response to TLR signaling differs, they exhibited similar metabolic changes. The results suggest that responsiveness of fibroblasts is altered in the context of obesity and insulin resistance and is controlled by the balance of AKT1/AKT2 activation, which may be critical to the development of hypertrophy.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dynamic control of autoreactive B cells from spontaneous germinal centers. 自发生发中心自身反应性B细胞的动态控制。

IF 3.4 3区医学

Journal of immunology Pub Date : 2025-10-01 DOI: 10.1093/jimmun/vkaf223

Kristine Oleinika, Alexia Correia Ferreira, Selma Mouftakir, Carlos Castrillon, Lisa Madungwe, Usha Nair, Facundo D Batista, Michael C Carroll

引用次数: 0

Gastrointestinal MAIT cells in chronic HIV-1 infection. 慢性HIV-1感染中的胃肠道MAIT细胞。

IF 3.4 3区医学

Journal of immunology Pub Date : 2025-09-30 DOI: 10.1093/jimmun/vkaf266

April L Ferre, Emily A Fehrman, Peter W Hunt, Ma Somsouk, Rebecca Hoh, Michael A Eller, Dominic Paquin-Proulx, Johan K Sandberg, Barbara L Shacklett

{"title":"Gastrointestinal MAIT cells in chronic HIV-1 infection.","authors":"April L Ferre, Emily A Fehrman, Peter W Hunt, Ma Somsouk, Rebecca Hoh, Michael A Eller, Dominic Paquin-Proulx, Johan K Sandberg, Barbara L Shacklett","doi":"10.1093/jimmun/vkaf266","DOIUrl":"https://doi.org/10.1093/jimmun/vkaf266","url":null,"abstract":"Mucosa-associated invariant T (MAIT) cells are innate-like T cells abundant in mucosal tissues, liver, and blood. MAIT cells recognize riboflavin metabolite-derived microbial antigens displayed by the MHC-I-related protein (MR1) and respond by producing cytokines, killing infected cells, and suppressing microbial growth. We previously demonstrated that MAIT cell numbers and function are reduced in chronic HIV-1, potentially increasing susceptibility to microbial coinfections. Here we assessed colorectal MAIT cells from people living with HIV-1 (PLWH, n = 36) and people without HIV-1 (PWOH, n = 22) by flow cytometry. In PBMCs, MAIT cells were less abundant in PLWH compared to PWOH. However, colorectal MAIT cell percentages were comparable in both groups, suggesting reduced loss from gut compared to blood in HIV-1 infection, or redistribution from blood to mucosae. In both groups, the majority of mucosal MAIT cells expressed CD8 and were enriched for CD8αα; a minority expressed CD4 or were double negative. Colorectal MAIT cells expressed CD69 and CD45RO, indicating a tissue-resident memory phenotype. Mucosal MAIT cells from PWOH expressed high perforin compared to PLWH, although granzyme B was low as compared to blood counterparts. Intracellular cytokine staining revealed robust cytokine production when stimulated with PMA/ionomycin. However, while blood MAIT cells responded strongly to inactivated Escherichia coli, mucosal MAIT cells responded poorly to this stimulus. Thus, gastrointestinal MAIT cells may be partially unresponsive toward commensal microbes, while remaining responsive to other stimuli. These findings provide novel insights into the functional profile of gastrointestinal MAIT cells in the context of chronic HIV-1.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MEF2D regulates T-cell function via CD70-CD27 signaling and promotes immune evasion in hepatocellular carcinoma. MEF2D通过CD70-CD27信号调节t细胞功能，促进肝细胞癌的免疫逃避。

IF 3.4 3区医学

Journal of immunology Pub Date : 2025-09-29 DOI: 10.1093/jimmun/vkaf228

Fanhua Kong, Liqing Wang, Zhongshan Lu, Jiakang Zhou, Qifa Ye, Wayne W Hancock, Yan Xiong

{"title":"MEF2D regulates T-cell function via CD70-CD27 signaling and promotes immune evasion in hepatocellular carcinoma.","authors":"Fanhua Kong, Liqing Wang, Zhongshan Lu, Jiakang Zhou, Qifa Ye, Wayne W Hancock, Yan Xiong","doi":"10.1093/jimmun/vkaf228","DOIUrl":"https://doi.org/10.1093/jimmun/vkaf228","url":null,"abstract":"Hepatocellular carcinoma (HCC) stands as one of the most prevalent and fatal malignancies globally, posing a persistent challenge in its treatment due to immune evasion. We knocked down MEF2D in HCC cell lines and analyzed HCC tissues and cell lines by RNA sequencing, Western blot, and immunohistochemistry. Chromatin immunoprecipitation was used to analyze the regulation of CD70 transcription by MEF2D. HCC cells with or without MEF2D knockout were injected into the livers of syngeneic BALB/c mice. Flow cytometry was used to analyze the function of T cells in tumors, spleens, and lymph nodes. We found that in contrast to wild-type tumors in immunocompetent mice, HCC with MEF2D knockdown had smaller tumors, increased T-cell activation, and impaired T regulatory (Treg) cell suppressive function. Mechanistically, MEF2D bound to the promoter region of CD70 gene and activated its transcription and this process was further enhanced by p300-induced MEF2D acetylation. CD70 blocking antibody inhibited activation of the CD70-CD27 signaling axis in murine HCC tumors, leading to impaired immunosuppressive function of Tregs and enhanced antitumor immunity. MEF2D blocks T-cell-mediated antitumor immunity by regulating the expression of CD70 and activating the CD70-CD27 signaling axis. Strategies to manipulate this pathway may improve the efficacy of liver cancer immunotherapy.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

H3K9 acetylation-NF-κB-AP-1 nexus targeted by ITE limits TNF-α-induced MMP-9 expression in monocytic cells. ITE靶向H3K9乙酰化- nf -κB-AP-1连接限制TNF-α-诱导的单核细胞MMP-9表达。

IF 3.4 3区医学

Journal of immunology Pub Date : 2025-09-27 DOI: 10.1093/jimmun/vkaf240

Fatemah Bahman, Shihab Kochumon, Md Zubbair Malik, Nadeem Akther, Sindhu Jacob, Hana Drobiova, Fahd Al-Mulla, Rasheed Ahmad

{"title":"H3K9 acetylation-NF-κB-AP-1 nexus targeted by ITE limits TNF-α-induced MMP-9 expression in monocytic cells.","authors":"Fatemah Bahman, Shihab Kochumon, Md Zubbair Malik, Nadeem Akther, Sindhu Jacob, Hana Drobiova, Fahd Al-Mulla, Rasheed Ahmad","doi":"10.1093/jimmun/vkaf240","DOIUrl":"https://doi.org/10.1093/jimmun/vkaf240","url":null,"abstract":"Matrix metalloproteinase 9 (MMP-9) plays a key role in the pathogenesis of inflammatory diseases and is upregulated by TNF-α. ITE (2-[1'H-indole-3'-carbonyl]-thiazole-4-carboxylic acid methyl ester) functions as an endogenous ligand for the aryl hydrocarbon receptor and is involved in inflammation. It is still uncertain whether ITE could affect TNF-α-induced MMP-9 expression in monocytic cells. In this study, we explored the effect of ITE on TNF-α-induced MMP-9 expression and the underlying mechanisms involved. Our results show that pretreatment of THP-1 monocytic cells with ITE significantly blocked TNF-α-induced MMP-9 expression at both the mRNA and protein secretion levels. Similar results were seen in primary human monocytes. The inhibition of MMP-9 by ITE occurs independently of TNFR1/2 modulation and apoptotic processes. RNA transcription data revealed that ITE suppresses the genes associated with inflammatory pathways. Mechanistically, histone modification profiling identified H3K9 acetylation as an epigenetic regulatory mark of TNF-α-induced MMP-9 expression. ChIP-qPCR data revealed that ITE pretreatment decreased TNF-α-triggered transcriptionally permissive acetylation marks at H3K9 in the MMP-9 promoter. Pharmacological inhibition of histone acetylation mimics the action of ITE in suppressing TNF-α-induced MMP-9 gene expression. Conversely, the acetylation induced by trichostatin A effectively reverses the inhibitory action of ITE. Moreover, increased TNF-α-induced binding of NF-κB or AP-1 at the MMP-9 promoter region was inhibited by ITE, resulting in suppression of MMP-9 gene expression. In conclusion, our study demonstrates that ITE reduces the TNF-α-induced MMP-9 expression via the H3K9 acetylation/NF-κB/AP-1 axis, highlighting a potential mechanism for mitigating MMP-9-related inflammatory disorders.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Foreign epitope-specific regulatory T cells respond robustly to vaccination and limit Th1 differentiation by conventional T cells specific for the same epitope. 外源表位特异性调节性T细胞对疫苗接种反应强烈，并限制了对相同表位特异性的常规T细胞的Th1分化。

IF 3.4 3区医学

Journal of immunology Pub Date : 2025-09-27 DOI: 10.1093/jimmun/vkaf254

Peter D Krueger, Kevin C Osum, Brian T Fife, Marc K Jenkins

{"title":"Foreign epitope-specific regulatory T cells respond robustly to vaccination and limit Th1 differentiation by conventional T cells specific for the same epitope.","authors":"Peter D Krueger, Kevin C Osum, Brian T Fife, Marc K Jenkins","doi":"10.1093/jimmun/vkaf254","DOIUrl":"https://doi.org/10.1093/jimmun/vkaf254","url":null,"abstract":"Foxp3+ regulatory T (Treg) cells with antigen receptors (TCRs) specific for host peptides suppress autoimmunity. Paradoxically, Treg cells are also found in CD4+ T-cell populations specific for foreign (nonhost) peptides. We investigated the origin and function of these Treg cells in mice. Populations of foreign peptide-specific naïve CD4+ T cells contained Foxp3- conventional (Tconv) and Foxp3+ Treg cells in about a 90:10 ratio. Both types of T cells proliferated in parallel after vaccination with the foreign peptide in incomplete or complete Fruend's adjuvants and formed memory cells. The Tconv population failed to express Foxp3, and formed Th1, Th17, and T follicular helper cells, whereas the Treg population largely retained Foxp3, and formed Th1- and Th17-like cells. The Treg cells specific for a foreign peptide had no effect on the proliferation of Tconv cells specific for that peptide but partially reduced Th1 cells in that population. Thus, foreign epitope-specific naïve Treg cells fine-tune the primary response of Tconv cells specific for the same epitope by curbing the Th1 fate while allowing a robust response.","PeriodicalId":16045,"journal":{"name":"Journal of immunology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0