The Journal of Immunology Author Choice最新文献_第3页

CD4-Transgenic Zebrafish Reveal Tissue-Resident Th2- and Regulatory T Cell–like Populations and Diverse Mononuclear Phagocytes cd4转基因斑马鱼揭示组织常驻Th2和调节性T细胞样群体和多样化的单核吞噬细胞

The Journal of Immunology Author Choice Pub Date : 2016-09-30 DOI: 10.4049/jimmunol.1600959

C. Dee, R. Nagaraju, E. Athanasiadis, C. Gray, Laura Fernandez del Ama, S. Johnston, C. Secombes, A. Cvejic, A. Hurlstone

{"title":"CD4-Transgenic Zebrafish Reveal Tissue-Resident Th2- and Regulatory T Cell–like Populations and Diverse Mononuclear Phagocytes","authors":"C. Dee, R. Nagaraju, E. Athanasiadis, C. Gray, Laura Fernandez del Ama, S. Johnston, C. Secombes, A. Cvejic, A. Hurlstone","doi":"10.4049/jimmunol.1600959","DOIUrl":"https://doi.org/10.4049/jimmunol.1600959","url":null,"abstract":"CD4+ T cells are at the nexus of the innate and adaptive arms of the immune system. However, little is known about the evolutionary history of CD4+ T cells, and it is unclear whether their differentiation into specialized subsets is conserved in early vertebrates. In this study, we have created transgenic zebrafish with vibrantly labeled CD4+ cells allowing us to scrutinize the development and specialization of teleost CD4+ leukocytes in vivo. We provide further evidence that CD4+ macrophages have an ancient origin and had already emerged in bony fish. We demonstrate the utility of this zebrafish resource for interrogating the complex behavior of immune cells at cellular resolution by the imaging of intimate contacts between teleost CD4+ T cells and mononuclear phagocytes. Most importantly, we reveal the conserved subspecialization of teleost CD4+ T cells in vivo. We demonstrate that the ancient and specialized tissues of the gills contain a resident population of il-4/13b–expressing Th2-like cells, which do not coexpress il-4/13a. Additionally, we identify a contrasting population of regulatory T cell–like cells resident in the zebrafish gut mucosa, in marked similarity to that found in the intestine of mammals. Finally, we show that, as in mammals, zebrafish CD4+ T cells will infiltrate melanoma tumors and obtain a phenotype consistent with a type 2 immune microenvironment. We anticipate that this unique resource will prove invaluable for future investigation of T cell function in biomedical research, the development of vaccination and health management in aquaculture, and for further research into the evolution of adaptive immunity.","PeriodicalId":310446,"journal":{"name":"The Journal of Immunology Author Choice","volume":"14 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125007316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 97

Dichotomy between T Cell and B Cell Tolerance to Neonatal Retroviral Infection Permits T Cell Therapy T细胞和B细胞对新生儿逆转录病毒感染耐受的二分法允许T细胞治疗

The Journal of Immunology Author Choice Pub Date : 2016-09-19 DOI: 10.4049/jimmunol.1600734

Bettina Mavrommatis, L. Baudino, Prisca Lévy, Julia Merkenschlager, U. Eksmond, T. Donnarumma, G. Young, J. Stoye, G. Kassiotis

{"title":"Dichotomy between T Cell and B Cell Tolerance to Neonatal Retroviral Infection Permits T Cell Therapy","authors":"Bettina Mavrommatis, L. Baudino, Prisca Lévy, Julia Merkenschlager, U. Eksmond, T. Donnarumma, G. Young, J. Stoye, G. Kassiotis","doi":"10.4049/jimmunol.1600734","DOIUrl":"https://doi.org/10.4049/jimmunol.1600734","url":null,"abstract":"Elucidation of the immune requirements for control or elimination of retroviral infection remains an important aim. We studied the induction of adaptive immunity to neonatal infection with a murine retrovirus, under conditions leading to immunological tolerance. We found that the absence of either maternal or offspring adaptive immunity permitted efficient vertical transmission of the retrovirus. Maternal immunodeficiency allowed the retrovirus to induce central Th cell tolerance in the infected offspring. In turn, this compromised the offspring’s ability to mount a protective Th cell–dependent B cell response. However, in contrast to T cells, offspring B cells were not centrally tolerized and retained their ability to respond to the infection when provided with T cell help. Thus, escape of retrovirus-specific B cells from deletional tolerance offers the opportunity to induce protective retroviral immunity by restoration of retrovirus-specific T cell help, suggesting similar T cell immunotherapies for persistent viral infections.","PeriodicalId":310446,"journal":{"name":"The Journal of Immunology Author Choice","volume":"72 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"124041761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Long-Lived CD4+IFN-γ+ T Cells rather than Short-Lived CD4+IFN-γ+IL-10+ T Cells Initiate Rapid IL-10 Production To Suppress Anamnestic T Cell Responses during Secondary Malaria Infection 在继发性疟疾感染期间，长寿命CD4+IFN-γ+ T细胞而非短寿命CD4+IFN-γ+IL-10+ T细胞启动快速IL-10产生抑制遗忘T细胞反应

The Journal of Immunology Author Choice Pub Date : 2016-09-14 DOI: 10.4049/jimmunol.1600968

A. Villegas‐Mendez, C. Inkson, Tovah N. Shaw, Patrick Strangward, K. Couper

{"title":"Long-Lived CD4+IFN-γ+ T Cells rather than Short-Lived CD4+IFN-γ+IL-10+ T Cells Initiate Rapid IL-10 Production To Suppress Anamnestic T Cell Responses during Secondary Malaria Infection","authors":"A. Villegas‐Mendez, C. Inkson, Tovah N. Shaw, Patrick Strangward, K. Couper","doi":"10.4049/jimmunol.1600968","DOIUrl":"https://doi.org/10.4049/jimmunol.1600968","url":null,"abstract":"CD4+ T cells that produce IFN-γ are the source of host-protective IL-10 during primary infection with a number of different pathogens, including Plasmodium spp. The fate of these CD4+IFN-γ+IL-10+ T cells following clearance of primary infection and their subsequent influence on the course of repeated infections is, however, presently unknown. In this study, utilizing IFN-γ–yellow fluorescent protein (YFP) and IL-10–GFP dual reporter mice, we show that primary malaria infection–induced CD4+YFP+GFP+ T cells have limited memory potential, do not stably express IL-10, and are disproportionately lost from the Ag-experienced CD4+ T cell memory population during the maintenance phase postinfection. CD4+YFP+GFP+ T cells generally exhibited a short-lived effector rather than effector memory T cell phenotype postinfection and expressed high levels of PD-1, Lag-3, and TIGIT, indicative of cellular exhaustion. Consistently, the surviving CD4+YFP+GFP+ T cell–derived cells were unresponsive and failed to proliferate during the early phase of secondary infection. In contrast, CD4+YFP+GFP− T cell–derived cells expanded rapidly and upregulated IL-10 expression during secondary infection. Correspondingly, CD4+ T cells were the major producers within an accelerated and amplified IL-10 response during the early stage of secondary malaria infection. Notably, IL-10 exerted quantitatively stronger regulatory effects on innate and CD4+ T cell responses during primary and secondary infections, respectively. The results in this study significantly improve our understanding of the durability of IL-10–producing CD4+ T cells postinfection and provide information on how IL-10 may contribute to optimized parasite control and prevention of immune-mediated pathology during repeated malaria infections.","PeriodicalId":310446,"journal":{"name":"The Journal of Immunology Author Choice","volume":"80 1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131229326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 25

Cathelicidins Have Direct Antiviral Activity against Respiratory Syncytial Virus In Vitro and Protective Function In Vivo in Mice and Humans 抗菌肽在体外对呼吸道合胞病毒具有直接抗病毒活性，并在小鼠和人体内具有保护作用

The Journal of Immunology Author Choice Pub Date : 2016-02-12 DOI: 10.4049/jimmunol.1502478

Silke M. Currie, Emily Gwyer Findlay, A. J. McFarlane, P. Fitch, B. Böttcher, N. Colegrave, A. Paras, A. Jóźwik, C. Chiu, J. Schwarze, D. Davidson

{"title":"Cathelicidins Have Direct Antiviral Activity against Respiratory Syncytial Virus In Vitro and Protective Function In Vivo in Mice and Humans","authors":"Silke M. Currie, Emily Gwyer Findlay, A. J. McFarlane, P. Fitch, B. Böttcher, N. Colegrave, A. Paras, A. Jóźwik, C. Chiu, J. Schwarze, D. Davidson","doi":"10.4049/jimmunol.1502478","DOIUrl":"https://doi.org/10.4049/jimmunol.1502478","url":null,"abstract":"Respiratory syncytial virus (RSV) is a leading cause of respiratory tract infection in infants, causing significant morbidity and mortality. No vaccine or specific, effective treatment is currently available. A more complete understanding of the key components of effective host response to RSV and novel preventative and therapeutic interventions are urgently required. Cathelicidins are host defense peptides, expressed in the inflamed lung, with key microbicidal and modulatory roles in innate host defense against infection. In this article, we demonstrate that the human cathelicidin LL-37 mediates an antiviral effect on RSV by inducing direct damage to the viral envelope, disrupting viral particles and decreasing virus binding to, and infection of, human epithelial cells in vitro. In addition, exogenously applied LL-37 is protective against RSV-mediated disease in vivo, in a murine model of pulmonary RSV infection, demonstrating maximal efficacy when applied concomitantly with virus. Furthermore, endogenous murine cathelicidin, induced by infection, has a fundamental role in protection against disease in vivo postinfection with RSV. Finally, higher nasal levels of LL-37 are associated with protection in a healthy human adult RSV infection model. These data lead us to propose that cathelicidins are a key, nonredundant component of host defense against pulmonary infection with RSV, functioning as a first point of contact antiviral shield and having additional later-phase roles in minimizing the severity of disease outcome. Consequently, cathelicidins represent an inducible target for preventative strategies against RSV infection and may inform the design of novel therapeutic analogs for use in established infection.","PeriodicalId":310446,"journal":{"name":"The Journal of Immunology Author Choice","volume":"19 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131789600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 109

Regulatory T Cells in Melanoma Revisited by a Computational Clustering of FOXP3+ T Cell Subpopulations 通过FOXP3+ T细胞亚群的计算聚类重新审视黑色素瘤中的调节性T细胞

The Journal of Immunology Author Choice Pub Date : 2016-02-10 DOI: 10.4049/jimmunol.1402695

H. Fujii, J. Josse, M. Tanioka, Y. Miyachi, François Husson, M. Ono

{"title":"Regulatory T Cells in Melanoma Revisited by a Computational Clustering of FOXP3+ T Cell Subpopulations","authors":"H. Fujii, J. Josse, M. Tanioka, Y. Miyachi, François Husson, M. Ono","doi":"10.4049/jimmunol.1402695","DOIUrl":"https://doi.org/10.4049/jimmunol.1402695","url":null,"abstract":"CD4+ T cells that express the transcription factor FOXP3 (FOXP3+ T cells) are commonly regarded as immunosuppressive regulatory T cells (Tregs). FOXP3+ T cells are reported to be increased in tumor-bearing patients or animals and are considered to suppress antitumor immunity, but the evidence is often contradictory. In addition, accumulating evidence indicates that FOXP3 is induced by antigenic stimulation and that some non-Treg FOXP3+ T cells, especially memory-phenotype FOXP3low cells, produce proinflammatory cytokines. Accordingly, the subclassification of FOXP3+ T cells is fundamental for revealing the significance of FOXP3+ T cells in tumor immunity, but the arbitrariness and complexity of manual gating have complicated the issue. In this article, we report a computational method to automatically identify and classify FOXP3+ T cells into subsets using clustering algorithms. By analyzing flow cytometric data of melanoma patients, the proposed method showed that the FOXP3+ subpopulation that had relatively high FOXP3, CD45RO, and CD25 expressions was increased in melanoma patients, whereas manual gating did not produce significant results on the FOXP3+ subpopulations. Interestingly, the computationally identified FOXP3+ subpopulation included not only classical FOXP3high Tregs, but also memory-phenotype FOXP3low cells by manual gating. Furthermore, the proposed method successfully analyzed an independent data set, showing that the same FOXP3+ subpopulation was increased in melanoma patients, validating the method. Collectively, the proposed method successfully captured an important feature of melanoma without relying on the existing criteria of FOXP3+ T cells, revealing a hidden association between the T cell profile and melanoma, and providing new insights into FOXP3+ T cells and Tregs.","PeriodicalId":310446,"journal":{"name":"The Journal of Immunology Author Choice","volume":"2 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2016-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125214548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 19

Mevalonate Biosynthesis Intermediates Are Key Regulators of Innate Immunity in Bovine Endometritis 甲羟戊酸生物合成中间体是牛子宫内膜炎先天免疫的关键调节因子

The Journal of Immunology Author Choice Pub Date : 2015-12-16 DOI: 10.4049/jimmunol.1501080

Gareth D Healey, C. Collier, Sholeem Griffin, H. Schuberth, O. Sandra, David G. Smith, S. Mahan, I. Dieuzy-Labaye, I. M. Sheldon

{"title":"Mevalonate Biosynthesis Intermediates Are Key Regulators of Innate Immunity in Bovine Endometritis","authors":"Gareth D Healey, C. Collier, Sholeem Griffin, H. Schuberth, O. Sandra, David G. Smith, S. Mahan, I. Dieuzy-Labaye, I. M. Sheldon","doi":"10.4049/jimmunol.1501080","DOIUrl":"https://doi.org/10.4049/jimmunol.1501080","url":null,"abstract":"Metabolic changes can influence inflammatory responses to bacteria. To examine whether localized manipulation of the mevalonate pathway impacts innate immunity, we exploited a unique mucosal disease model, endometritis, where inflammation is a consequence of innate immunity. IL responses to pathogenic bacteria and LPS were modulated in bovine endometrial cell and organ cultures by small molecules that target the mevalonate pathway. Treatment with multiple statins, bisphosphonates, squalene synthase inhibitors, and small interfering RNA showed that inhibition of farnesyl-diphosphate farnesyl transferase (squalene synthase), but not 3-hydroxy-3-methylglutaryl-CoA reductase or farnesyl diphosphate synthase, reduced endometrial organ and cellular inflammatory responses to pathogenic bacteria and LPS. Although manipulation of the mevalonate pathway reduced cellular cholesterol, impacts on inflammation were independent of cholesterol concentration as cholesterol depletion using cyclodextrins did not alter inflammatory responses. Treatment with the isoprenoid mevalonate pathway-intermediates, farnesyl diphosphate and geranylgeranyl diphosphate, also reduced endometrial cellular inflammatory responses to LPS. These data imply that manipulating the mevalonate pathway regulates innate immunity within the endometrium, and that isoprenoids are regulatory molecules in this process, knowledge that could be exploited for novel therapeutic strategies.","PeriodicalId":310446,"journal":{"name":"The Journal of Immunology Author Choice","volume":"14 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129416604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 17

Synovial Regulatory T Cells Occupy a Discrete TCR Niche in Human Arthritis and Require Local Signals To Stabilize FOXP3 Protein Expression 滑膜调节性T细胞在人类关节炎中占据离散的TCR小生境，并需要局部信号来稳定FOXP3蛋白的表达

The Journal of Immunology Author Choice Pub Date : 2015-11-11 DOI: 10.4049/jimmunol.1500391

D. Bending, E. Giannakopoulou, H. Lom, L. Wedderburn

{"title":"Synovial Regulatory T Cells Occupy a Discrete TCR Niche in Human Arthritis and Require Local Signals To Stabilize FOXP3 Protein Expression","authors":"D. Bending, E. Giannakopoulou, H. Lom, L. Wedderburn","doi":"10.4049/jimmunol.1500391","DOIUrl":"https://doi.org/10.4049/jimmunol.1500391","url":null,"abstract":"Although there is great interest in harnessing the immunosuppressive potential of FOXP3+ regulatory T cells (Tregs) for treating autoimmunity, a sizeable knowledge gap exists regarding Treg fate in human disease. In juvenile idiopathic arthritis (JIA) patients, we have previously reported that atypical CD25+FOXP3− Treg-like cells uniquely populate the inflamed site. Intriguingly, their proportions relative to CD25+FOXP3+ Tregs associate with arthritis course, suggesting a role in disease. The ontogeny of these FOXP3− Treg-like cells is, however, unknown. In this study, we interrogated clonal relationships between CD4+ T cell subsets in JIA, using high-throughput TCR repertoire analysis. We reveal that FOXP3+ Tregs possess highly exclusive TCRβ usage from conventional T cells, in blood, and also at the inflamed site, where they are clonally expanded. Intriguingly, the repertoires of FOXP3+ Tregs in synovial fluid are highly overlapping with CD25+FOXP3− Treg-like cells, indicating fluctuations in FOXP3 expression in the inflamed joint. Furthermore, cultured synovial Tregs rapidly downregulated FOXP3 protein (but not mRNA), and this process was prevented by addition of synovial fluid from JIA patients, through an IL-6–independent mechanism. Our findings suggest that most Tregs arise from a separate lineage from conventional T cells, and that this repertoire divergence is largely maintained under chronic inflammatory conditions. We propose that subsequent Treg expansions at the inflamed site creates an environment that leads to competition for limited resources within the synovium, resulting in the destabilization of FOXP3 expression in some Tregs.","PeriodicalId":310446,"journal":{"name":"The Journal of Immunology Author Choice","volume":"195 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2015-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129065296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 24

Enhanced Detection of Antigen-Specific CD4+ T Cells Using Altered Peptide Flanking Residue Peptide–MHC Class II Multimers 利用改变的肽侧残基肽- mhc II类多聚体增强抗原特异性CD4+ T细胞的检测

The Journal of Immunology Author Choice Pub Date : 2015-11-09 DOI: 10.4049/jimmunol.1402787

C. Holland, G. Dolton, M. Scurr, K. Ladell, Andrea Schauenburg, K. Miners, Florian Madura, A. Sewell, D. Price, D. Cole, A. Godkin

引用次数: 11